2017

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Open AccessArticle Effects of Titanium Mesh Surfaces-Coated with Hydroxyapatite/β-Tricalcium Phosphate Nanotubes on Acetabular Bone Defects in Rabbits

by Thuy-Duong Thi Nguyen, Tae-Sung Bae, Dae-hyeok Yang, Myung-sik Park and Sun-jung Yoon

Int. J. Mol. Sci. 2017, 18(7), 1462; doi:10.3390/ijms18071462

Received: 27 May 2017 / Revised: 23 June 2017 / Accepted: 4 July 2017 / Published: 7 July 2017

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Abstract

The management of severe acetabular bone defects in revision reconstructive orthopedic surgery is challenging. In this study, cyclic precalcification (CP) treatment was used on both nanotube-surface Ti-mesh and a bone graft substitute for the acetabular defect model, and its effects were assessed in

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The management of severe acetabular bone defects in revision reconstructive orthopedic surgery is challenging. In this study, cyclic precalcification (CP) treatment was used on both nanotube-surface Ti-mesh and a bone graft substitute for the acetabular defect model, and its effects were assessed in vitro and in vivo. Nanotube-Ti mesh coated with hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) was manufactured by an anodizing and a sintering method, respectively. An 8 mm diameter defect was created on each acetabulum of eight rabbits, then treated by grafting materials and covered by Ti meshes. At four and eight weeks, postoperatively, biopsies were performed for histomorphometric analyses. The newly-formed bone layers under cyclic precalcified anodized Ti (CP-AT) meshes were superior with regard to the mineralized area at both four and eight weeks, as compared with that under untreated Ti meshes. Active bone regeneration at 2–4 weeks was stronger than at 6–8 weeks, particularly with treated biphasic ceramic (p < 0.05). CP improved the bioactivity of Ti meshes and biphasic grafting materials. Moreover, the precalcified nanotubular Ti meshes could enhance early contact bone formation on the mesh and, therefore, may reduce the collapse of Ti meshes into the defect, increasing the sufficiency of acetabular reconstruction. Finally, cyclic precalcification did not affect bone regeneration by biphasic grafting materials in vivo. Full article

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Open AccessArticle Prevention of Oxidized Low Density Lipoprotein-Induced Endothelial Cell Injury by DA-PLGA-PEG-cRGD Nanoparticles Combined with Ultrasound

by Zhaojun Li, Hui Huang, Lili Huang, Lianfang Du, Ying Sun and Yourong Duan

Int. J. Mol. Sci. 2017, 18(4), 815; doi:10.3390/ijms18040815

Received: 21 February 2017 / Revised: 6 April 2017 / Accepted: 7 April 2017 / Published: 13 April 2017

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Abstract

In general, atherosclerosis is considered to be a form of chronic inflammation. Dexamethasone has anti-inflammatory effects in atherosclerosis, but it was not considered for long-term administration on account of a poor pharmacokinetic profile and adverse side effects. Nanoparticles in which drugs can be

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In general, atherosclerosis is considered to be a form of chronic inflammation. Dexamethasone has anti-inflammatory effects in atherosclerosis, but it was not considered for long-term administration on account of a poor pharmacokinetic profile and adverse side effects. Nanoparticles in which drugs can be dissolved, encapsulated, entrapped or chemically attached to the particle surface have abilities to incorporate dexamethasone and to be used as controlled or targeted drug delivery system. Long circulatory polymeric nanoparticles present as an assisting approach for controlled and targeted release of the encapsulated drug at the atherosclerotic site. Polymeric nanoparticles combined with ultrasound (US) are widely applied in cancer treatment due to their time applications, low cost, simplicity, and safety. However, there are few studies on atherosclerosis treatment using polymeric nanoparticles combined with US. In this study, targeted dexamethasone acetate (DA)-loaded poly (lactide-glycolide)-polyethylene glycol-cRGD (PLGA-PEG-cRGD) nanoparticles (DA-PLGA-PEG-cRGD NPs) were prepared by the emulsion-evaporation method using cRGD modified PLGA-PEG polymeric materials (PLGA-PEG-cRGD) prepared as the carrier. The average particle size of DA-PLGA-PEG-cRGD NPs was 221.6 ± 0.9 nm. Morphology of the nanoparticles was spherical and uniformly dispersed. In addition, the DA released profiles suggested that ultrasound could promote drug release from the nanocarriers and accelerate the rate of release. In vitro, the cellular uptake process of fluorescein isothiocyanate (FITC)@DA-PLGA-PEG-cRGD NPs combined with US into the damaged human umbilical vein endothelial cells (HUVECs) indicated that US promoted rapid intracellular uptake of FITC@DA- PLGA-PEG-cRGD NPs. The cell viability of DA-PLGA-PEG-cRGD NPs combined with US reached 91.9% ± 0.2%, which demonstrated that DA-PLGA-PEG-cRGD NPs combined with US had a positive therapeutic effect on damaged HUVECs. Overall, DA-PLGA-PEG-cRGD NPs in combination with US may provide a promising drug delivery system to enhance the therapeutic effects of these chemotherapeutics at the cellular level. Full article

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Open AccessArticle Bioactivity of NANOZR Induced by Alkali Treatment

by Mariko Nishizaki, Satoshi Komasa, Yoichiro Taguchi, Hiroshi Nishizaki and Joji Okazaki

Int. J. Mol. Sci. 2017, 18(4), 780; doi:10.3390/ijms18040780

Received: 7 March 2017 / Revised: 28 March 2017 / Accepted: 2 April 2017 / Published: 6 April 2017

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Abstract

In recent years, zirconia has been a recognized implant material in clinical dentistry. In the present study, we investigated the performance of an alkali-modified ceria-stabilized tetragonal ZrO₂ polycrystalline ceramic-based nanostructured zirconia/alumina composite (NANOZR) implant by assessing surface morphology and composition, wettability, bovine

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In recent years, zirconia has been a recognized implant material in clinical dentistry. In the present study, we investigated the performance of an alkali-modified ceria-stabilized tetragonal ZrO₂ polycrystalline ceramic-based nanostructured zirconia/alumina composite (NANOZR) implant by assessing surface morphology and composition, wettability, bovine serum albumin adsorption rate, rat bone marrow (RBM) cell attachment, and capacity for inducing bone differentiation. NANOZR surfaces without and with alkali treatment served as the control and test groups, respectively. RBM cells were seeded in a microplate with the implant and cultured in osteogenic differentiation medium, and their differentiation was evaluated by measuring alkaline phosphatase (ALP) activity, osteocalcin (OCN) production, calcium deposition, and osteogenic gene expression. The alkali-treated NANOZR surface increased ALP activity, OCN production, calcium deposition, and osteogenesis-related gene expression in attached RBM cells. These data suggest that alkali treatment enhances the osteogenesis-inducing capacity of NANOZR implants and may therefore improve their biointegration into alveolar bone. Full article

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Open AccessArticle Effects of Silver Nanoparticles on Multiple Drug-Resistant Strains of Staphylococcus aureus and Pseudomonas aeruginosa from Mastitis-Infected Goats: An Alternative Approach for Antimicrobial Therapy

by Yu-Guo Yuan, Qiu-Ling Peng and Sangiliyandi Gurunathan

Int. J. Mol. Sci. 2017, 18(3), 569; doi:10.3390/ijms18030569

Received: 28 December 2016 / Revised: 16 February 2017 / Accepted: 18 February 2017 / Published: 6 March 2017

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Abstract

Recently, silver nanoparticles (AgNPs) have been widely used in various applications as antimicrobial agents, anticancer, diagnostics, biomarkers, cell labels, and drug delivery systems for the treatment of various diseases. Microorganisms generally acquire resistance to antibiotics through the course of antibacterial therapy. Multi-drug resistance

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Recently, silver nanoparticles (AgNPs) have been widely used in various applications as antimicrobial agents, anticancer, diagnostics, biomarkers, cell labels, and drug delivery systems for the treatment of various diseases. Microorganisms generally acquire resistance to antibiotics through the course of antibacterial therapy. Multi-drug resistance (MDR) has become a growing problem in the treatment of infectious diseases, and the widespread use of broad-spectrum antibiotics has resulted in the development of antibiotic resistance by numerous human and animal bacterial pathogens. As a result, an increasing number of microorganisms are resistant to multiple antibiotics causing continuing economic losses in dairy farming. Therefore, there is an urgent need for the development of alternative, cost-effective, and efficient antimicrobial agents that overcome antimicrobial resistance. Here, AgNPs synthesized using the bio-molecule quercetin were characterized using various analytical techniques. The synthesized AgNPs were highly spherical in shape and had an average size of 11 nm. We evaluated the efficacy of synthesized AgNPs against two MDR pathogenic bacteria, namely, Pseudomonas aeruginosa and Staphylococcus aureus, which were isolated from milk samples produced by mastitis-infected goats. The minimum inhibitory concentrations (MICs) of AgNPs against P. aeruginosa and S. aureus were found to be 1 and 2 μg/mL, respectively. Our findings suggest that AgNPs exert antibacterial effects in a dose- and time-dependent manner. Results from the present study demonstrate that the antibacterial activity of AgNPs is due to the generation of reactive oxygen species (ROS), malondialdehyde (MDA), and leakage of proteins and sugars in bacterial cells. Results of the present study showed that AgNP-treated bacteria had significantly lower lactate dehydrogenase activity (LDH) and lower adenosine triphosphate (ATP) levels compared to the control. Furthermore, AgNP-treated bacteria showed downregulated expression of glutathione (GSH), upregulation of glutathione S-transferase (GST), and downregulation of both superoxide dismutase (SOD) and catalase (CAT). These physiological and biochemical measurements were consistently observed in AgNP-treated bacteria, thereby suggesting that AgNPs can induce bacterial cell death. Thus, the above results represent conclusive findings on the mechanism of action of AgNPs against different types of bacteria. This study also demonstrates the promising use of nanoparticles as antibacterial agents for use in the biotechnology and biomedical industry. Furthermore, this study is the first to propose the mode of action of AgNPs against MDR pathogens isolated from goats infected with subclinical mastitis. Full article

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Open AccessArticle Photoluminescent Gold Nanoclusters in Cancer Cells: Cellular Uptake, Toxicity, and Generation of Reactive Oxygen Species

by Marija Matulionyte, Dominyka Dapkute, Laima Budenaite, Greta Jarockyte and Ricardas Rotomskis

Int. J. Mol. Sci. 2017, 18(2), 378; doi:10.3390/ijms18020378

Received: 5 October 2016 / Revised: 26 January 2017 / Accepted: 2 February 2017 / Published: 10 February 2017

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Abstract

In recent years, photoluminescent gold nanoclusters have attracted considerable interest in both fundamental biomedical research and practical applications. Due to their ultrasmall size, unique molecule-like optical properties, and facile synthesis gold nanoclusters have been considered very promising photoluminescent agents for biosensing, bioimaging, and

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In recent years, photoluminescent gold nanoclusters have attracted considerable interest in both fundamental biomedical research and practical applications. Due to their ultrasmall size, unique molecule-like optical properties, and facile synthesis gold nanoclusters have been considered very promising photoluminescent agents for biosensing, bioimaging, and targeted therapy. Yet, interaction of such ultra-small nanoclusters with cells and other biological objects remains poorly understood. Therefore, the assessment of the biocompatibility and potential toxicity of gold nanoclusters is of major importance before their clinical application. In this study, the cellular uptake, cytotoxicity, and intracellular generation of reactive oxygen species (ROS) of bovine serum albumin-encapsulated (BSA-Au NCs) and 2-(N-morpholino) ethanesulfonic acid (MES)capped photoluminescent gold nanoclusters (Au-MES NCs) were investigated. The results showed that BSA-Au NCs accumulate in cells in a similar manner as BSA alone, indicating an endocytotic uptake mechanism while ultrasmall Au-MES NCs were distributed homogeneously throughout the whole cell volume including cell nucleus. The cytotoxicity of BSA-Au NCs was negligible, demonstrating good biocompatibility of such BSA-protected Au NCs. In contrast, possibly due to ultrasmall size and thin coating layer, Au-MES NCs exhibited exposure time-dependent high cytotoxicity and higher reactivity which led to highly increased generation of reactive oxygen species. The results demonstrate the importance of the coating layer to biocompatibility and toxicity of ultrasmall photoluminescent gold nanoclusters. Full article

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Open AccessReview The Current State of Nanoparticle-Induced Macrophage Polarization and Reprogramming Research

by Xiaoyuan Miao, Xiangfeng Leng and Qiu Zhang

Int. J. Mol. Sci. 2017, 18(2), 336; doi:10.3390/ijms18020336

Received: 9 December 2016 / Revised: 20 January 2017 / Accepted: 2 February 2017 / Published: 6 February 2017

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Abstract

Macrophages are vital regulators of the host defense in organisms. In response to different local microenvironments, resting macrophages (M0) can be polarized into different phenotypes, pro-inflammatory (M1) or anti-inflammatory (M2), and perform different roles in different physiological or pathological conditions. Polarized macrophages can

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Macrophages are vital regulators of the host defense in organisms. In response to different local microenvironments, resting macrophages (M0) can be polarized into different phenotypes, pro-inflammatory (M1) or anti-inflammatory (M2), and perform different roles in different physiological or pathological conditions. Polarized macrophages can also be further reprogrammed by reversing their phenotype according to the changed milieu. Macrophage polarization and reprogramming play essential roles in maintaining the steady state of the immune system and are involved in the processes of many diseases. As foreign substances, nanoparticles (NPs) mainly target macrophages after entering the body. NPs can perturb the polarization and reprogramming of macrophages, affect their immunological function and, therefore, affect the pathological process of disease. Optimally-designed NPs for the modulation of macrophage polarization and reprogramming might provide new solutions for treating diseases. Systematically investigating how NPs affect macrophage polarization is crucial for understanding the regulatory effects of NPs on immune cells in vivo. In this review, macrophage polarization by NPs is summarized and discussed. Full article

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Open AccessReview The Role of Reactive Oxygen Species (ROS) in the Biological Activities of Metallic Nanoparticles

by Ahmed Abdal Dayem, Mohammed Kawser Hossain, Soo Bin Lee, Kyeongseok Kim, Subbroto Kumar Saha, Gwang-Mo Yang, Hye Yeon Choi and Ssang-Goo Cho

Int. J. Mol. Sci. 2017, 18(1), 120; doi:10.3390/ijms18010120

Received: 25 November 2016 / Revised: 27 December 2016 / Accepted: 4 January 2017 / Published: 10 January 2017

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Abstract

Nanoparticles (NPs) possess unique physical and chemical properties that make them appropriate for various applications. The structural alteration of metallic NPs leads to different biological functions, specifically resulting in different potentials for the generation of reactive oxygen species (ROS). The amount of ROS

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Nanoparticles (NPs) possess unique physical and chemical properties that make them appropriate for various applications. The structural alteration of metallic NPs leads to different biological functions, specifically resulting in different potentials for the generation of reactive oxygen species (ROS). The amount of ROS produced by metallic NPs correlates with particle size, shape, surface area, and chemistry. ROS possess multiple functions in cellular biology, with ROS generation a key factor in metallic NP-induced toxicity, as well as modulation of cellular signaling involved in cell death, proliferation, and differentiation. In this review, we briefly explained NP classes and their biomedical applications and describe the sources and roles of ROS in NP-related biological functions in vitro and in vivo. Furthermore, we also described the roles of metal NP-induced ROS generation in stem cell biology. Although the roles of ROS in metallic NP-related biological functions requires further investigation, modulation and characterization of metallic NP-induced ROS production are promising in the application of metallic NPs in the areas of regenerative medicine and medical devices. Full article

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2016

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Open AccessArticle Multifunctional Composite Microcapsules for Oral Delivery of Insulin

by Shaoping Sun, Na Liang, Xianfeng Gong, Weiwei An, Yoshiaki Kawashima, Fude Cui and Pengfei Yan

Int. J. Mol. Sci. 2017, 18(1), 54; doi:10.3390/ijms18010054

Received: 7 November 2016 / Revised: 11 December 2016 / Accepted: 21 December 2016 / Published: 28 December 2016

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Abstract

In this study, we designed and developed a new drug delivery system of multifunctional composite microcapsules for oral administration of insulin. Firstly, in order to enhance the encapsulation efficiency, insulin was complexed with functional sodium deoxycholate to form insulin-sodium deoxycholate complex using hydrophobic

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In this study, we designed and developed a new drug delivery system of multifunctional composite microcapsules for oral administration of insulin. Firstly, in order to enhance the encapsulation efficiency, insulin was complexed with functional sodium deoxycholate to form insulin-sodium deoxycholate complex using hydrophobic ion pairing method. Then the complex was encapsulated into poly(lactide-co-glycolide) (PLGA) nanoparticles by emulsion solvent diffusion method. The PLGA nanoparticles have a mean size of 168 nm and a zeta potential of −29.2 mV. The encapsulation efficiency was increased to 94.2% for the complex. In order to deliver insulin to specific gastrointestinal regions and reduce the burst release of insulin from PLGA nanoparticles, hence enhancing the bioavailability of insulin, enteric targeting multifunctional composite microcapsules were further prepared by encapsulating PLGA nanoparticles into pH-sensitive hydroxypropyl methyl cellulose phthalate (HP55) using organic spray-drying method. A pH-dependent insulin release profile was observed for this drug delivery system in vitro. All these strategies help to enhance the encapsulation efficiency, control the drug release, and protect insulin from degradation. In diabetic fasted rats, administration of the composite microcapsules produced a great enhancement in the relative bioavailability, which illustrated that this formulation was an effective candidate for oral insulin delivery. Full article

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Open AccessArticle Differential Cytotoxic Potential of Silver Nanoparticles in Human Ovarian Cancer Cells and Ovarian Cancer Stem Cells

by Yun-Jung Choi, Jung-Hyun Park, Jae Woong Han, Eunsu Kim, Oh Jae-Wook, Seung Yoon Lee, Jin-Hoi Kim and Sangiliyandi Gurunathan

Int. J. Mol. Sci. 2016, 17(12), 2077; doi:10.3390/ijms17122077

Received: 9 September 2016 / Revised: 17 November 2016 / Accepted: 30 November 2016 / Published: 12 December 2016

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Abstract

The cancer stem cell (CSC) hypothesis postulates that cancer cells are composed of hierarchically-organized subpopulations of cells with distinct phenotypes and tumorigenic capacities. As a result, CSCs have been suggested as a source of disease recurrence. Recently, silver nanoparticles (AgNPs) have been used

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The cancer stem cell (CSC) hypothesis postulates that cancer cells are composed of hierarchically-organized subpopulations of cells with distinct phenotypes and tumorigenic capacities. As a result, CSCs have been suggested as a source of disease recurrence. Recently, silver nanoparticles (AgNPs) have been used as antimicrobial, disinfectant, and antitumor agents. However, there is no study reporting the effects of AgNPs on ovarian cancer stem cells (OvCSCs). In this study, we investigated the cytotoxic effects of AgNPs and their mechanism of causing cell death in A2780 (human ovarian cancer cells) and OvCSCs derived from A2780. In order to examine these effects, OvCSCs were isolated and characterized using positive CSC markers including aldehyde dehydrogenase (ALDH) and CD133 by fluorescence-activated cell sorting (FACS). The anticancer properties of the AgNPs were evaluated by assessing cell viability, leakage of lactate dehydrogenase (LDH), reactive oxygen species (ROS), and mitochondrial membrane potential (mt-MP). The inhibitory effect of AgNPs on the growth of ovarian cancer cells and OvCSCs was evaluated using a clonogenic assay. Following 1–2 weeks of incubation with the AgNPs, the numbers of A2780 (bulk cells) and ALDH⁺/CD133⁺ colonies were significantly reduced. The expression of apoptotic and anti-apoptotic genes was measured by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Our observations showed that treatment with AgNPs resulted in severe cytotoxicity in both ovarian cancer cells and OvCSCs. In particular, AgNPs showed significant cytotoxic potential in ALDH⁺/CD133⁺ subpopulations of cells compared with other subpopulation of cells and also human ovarian cancer cells (bulk cells). These findings suggest that AgNPs can be utilized in the development of novel nanotherapeutic molecules for the treatment of ovarian cancers by specific targeting of the ALDH⁺/CD133⁺ subpopulation of cells. Full article

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Open AccessArticle Synthesis of Non-Toxic Silica Particles Stabilized by Molecular Complex Oleic-Acid/Sodium Oleate

by Catalin Ilie Spataru, Raluca Ianchis, Cristian Petcu, Cristina Lavinia Nistor, Violeta Purcar, Bogdan Trica, Sabina Georgiana Nitu, Raluca Somoghi, Elvira Alexandrescu, Florin Oancea and Dan Donescu

Int. J. Mol. Sci. 2016, 17(11), 1936; doi:10.3390/ijms17111936

Received: 21 October 2016 / Revised: 11 November 2016 / Accepted: 15 November 2016 / Published: 19 November 2016

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Abstract

The present work is focused on the preparation of biocompatible silica particles from sodium silicate, stabilized by a vesicular system containing oleic acid (OLA) and its alkaline salt (OLANa). Silica nanoparticles were generated by the partial neutralization of oleic acid (OLA), with the

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The present work is focused on the preparation of biocompatible silica particles from sodium silicate, stabilized by a vesicular system containing oleic acid (OLA) and its alkaline salt (OLANa). Silica nanoparticles were generated by the partial neutralization of oleic acid (OLA), with the sodium cation present in the aqueous solutions of sodium silicate. At the molar ratio OLA/Na⁺ = 2:1, the molar ratio (OLA/OLANa = 1:1) required to form vesicles, in which the carboxyl and carboxylate groups have equal concentrations, was achieved. In order to obtain hydrophobically modified silica particles, octadecyltriethoxysilane (ODTES) was added in a sodium silicate sol–gel mixture at different molar ratios. The interactions between the octadecyl groups from the modified silica and the oleyl chains from the OLA/OLANa stabilizing system were investigated via simultaneous thermogravimetry (TG) and differential scanning calorimetry (DSC) (TG-DSC) analyses.A significant decrease in vaporization enthalpy and an increase in amount of ODTES were observed. Additionally, that the hydrophobic interaction between OLA and ODTES has a strong impact on the hybrids’ final morphology and on their textural characteristics was revealed. The highest hydrodynamic average diameter and the most negative ζ potential were recorded for the hybrid in which the ODTES/sodium silicate molar ratio was 1:5. The obtained mesoporous silica particles, stabilized by the OLA/OLANa vesicular system, may find application as carriers for hydrophobic bioactive molecules. Full article

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Open AccessReview Silver Nanoparticles: Synthesis, Characterization, Properties, Applications, and Therapeutic Approaches

by Xi-Feng Zhang, Zhi-Guo Liu, Wei Shen and Sangiliyandi Gurunathan

Int. J. Mol. Sci. 2016, 17(9), 1534; doi:10.3390/ijms17091534

Received: 5 July 2016 / Revised: 19 August 2016 / Accepted: 1 September 2016 / Published: 13 September 2016

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Abstract

Recent advances in nanoscience and nanotechnology radically changed the way we diagnose, treat, and prevent various diseases in all aspects of human life. Silver nanoparticles (AgNPs) are one of the most vital and fascinating nanomaterials among several metallic nanoparticles that are involved in

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Recent advances in nanoscience and nanotechnology radically changed the way we diagnose, treat, and prevent various diseases in all aspects of human life. Silver nanoparticles (AgNPs) are one of the most vital and fascinating nanomaterials among several metallic nanoparticles that are involved in biomedical applications. AgNPs play an important role in nanoscience and nanotechnology, particularly in nanomedicine. Although several noble metals have been used for various purposes, AgNPs have been focused on potential applications in cancer diagnosis and therapy. In this review, we discuss the synthesis of AgNPs using physical, chemical, and biological methods. We also discuss the properties of AgNPs and methods for their characterization. More importantly, we extensively discuss the multifunctional bio-applications of AgNPs; for example, as antibacterial, antifungal, antiviral, anti-inflammatory, anti-angiogenic, and anti-cancer agents, and the mechanism of the anti-cancer activity of AgNPs. In addition, we discuss therapeutic approaches and challenges for cancer therapy using AgNPs. Finally, we conclude by discussing the future perspective of AgNPs. Full article

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Open AccessArticle A Novel Prostate-Specific Membrane-Antigen (PSMA) Targeted Micelle-Encapsulating Wogonin Inhibits Prostate Cancer Cell Proliferation via Inducing Intrinsic Apoptotic Pathway

by Hailong Zhang, Xiaogang Liu, Fengbo Wu, Feifei Qin, Ping Feng, Ting Xu, Xiang Li and Li Yang

Int. J. Mol. Sci. 2016, 17(5), 676; doi:10.3390/ijms17050676

Received: 29 March 2016 / Revised: 21 April 2016 / Accepted: 25 April 2016 / Published: 17 May 2016

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Abstract

Prostate cancer (PCa) is a malignant tumor for which there are no effective treatment strategies. In this study, we developed a targeted strategy for prostate-specific membrane-antigen (PSMA)-positive PCa in vitro based on 2-(3-((S)-5-amino-1-carboxypentyl)ureido) pentanedioic acid (ACUPA) modified polyethylene glycol (PEG)-Cholesterol micelles

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Prostate cancer (PCa) is a malignant tumor for which there are no effective treatment strategies. In this study, we developed a targeted strategy for prostate-specific membrane-antigen (PSMA)-positive PCa in vitro based on 2-(3-((S)-5-amino-1-carboxypentyl)ureido) pentanedioic acid (ACUPA) modified polyethylene glycol (PEG)-Cholesterol micelles containing wogonin (WOG), which was named ACUPA-M-WOG. ACUPA-M-WOG was conventionally prepared using a self-assembling method, which produced stable particle size and ζ potential. Moreover, ACUPA-M-WOG showed good drug encapsulating capacity and drug release profiles. Fluorescence activated cell sorting (FACS) results suggested that ACUPA modified PEG-Cholesterol micelles could effectively enhance the drug uptake on PSMA(+) PCa cells, and the cytotoxicity of ACUPA-M-WOG was stronger than other controls according to in vitro cellular proliferation and apoptosis assays, separately through methyl thiazolyl tetrazolium (MTT) and Annexin V/Propidium Iodide (PI) staining. Finally, the molecular mechanisms of ACUPA-M-WOG’s effects on human PSMA(+) PCa were investigated, and were mainly the intrinsic or extrinsic apoptosis signaling pathways. The Western blot results suggested that ACUPA-M-WOG could enhance the WOG-induced apoptosis, which was mainly via the intrinsic signaling pathway rather than the extrinsic signaling pathway. In conclusion, ACUPA-M-WOG was successfully developed for WOG-selective delivery to PSMA(+) PCa cells and had stronger inhibition than free drugs, which might make it an effective strategy for PSMA(+) PCa. Full article

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Open AccessArticle The Isolation of DNA by Polycharged Magnetic Particles: An Analysis of the Interaction by Zeta Potential and Particle Size

by Yazan Haddad, Kledi Xhaxhiu, Pavel Kopel, David Hynek, Ondrej Zitka and Vojtech Adam

Int. J. Mol. Sci. 2016, 17(4), 550; doi:10.3390/ijms17040550

Received: 25 February 2016 / Revised: 30 March 2016 / Accepted: 7 April 2016 / Published: 20 April 2016

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Abstract

Magnetic isolation of biological targets is in major demand in the biotechnology industry today. This study considers the interaction of four surface-modified magnetic micro- and nanoparticles with selected DNA fragments. Different surface modifications of nanomaghemite precursors were investigated: MAN37 (silica-coated), MAN127 (polyvinylpyrrolidone-coated), MAN158

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Magnetic isolation of biological targets is in major demand in the biotechnology industry today. This study considers the interaction of four surface-modified magnetic micro- and nanoparticles with selected DNA fragments. Different surface modifications of nanomaghemite precursors were investigated: MAN37 (silica-coated), MAN127 (polyvinylpyrrolidone-coated), MAN158 (phosphate-coated), and MAN164 (tripolyphosphate-coated). All particles were positive polycharged agglomerated monodispersed systems. Mean particle sizes were 0.48, 2.97, 2.93, and 3.67 μm for MAN37, MAN127, MAN164, and MAN158, respectively. DNA fragments exhibited negative zeta potential of −0.22 mV under binding conditions (high ionic strength, low pH, and dehydration). A decrease in zeta potential of particles upon exposure to DNA was observed with exception of MAN158 particles. The measured particle size of MAN164 particles increased by nearly twofold upon exposure to DNA. Quantitative PCR isolation of DNA with a high retrieval rate was observed by magnetic particles MAN127 and MAN164. Interaction between polycharged magnetic particles and DNA is mediated by various binding mechanisms such as hydrophobic and electrostatic interactions. Future development of DNA isolation technology requires an understanding of the physical and biochemical conditions of this process. Full article

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Open AccessArticle A RNA-DNA Hybrid Aptamer for Nanoparticle-Based Prostate Tumor Targeted Drug Delivery

by John C. Leach, Andrew Wang, Kaiming Ye and Sha Jin

Int. J. Mol. Sci. 2016, 17(3), 380; doi:10.3390/ijms17030380

Received: 17 February 2016 / Revised: 8 March 2016 / Accepted: 10 March 2016 / Published: 14 March 2016

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Abstract

The side effects of radio- and chemo-therapy pose long-term challenges on a cancer patient’s health. It is, therefore, highly desirable to develop more effective therapies that can specifically target carcinoma cells without damaging normal and healthy cells. Tremendous efforts have been made in

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The side effects of radio- and chemo-therapy pose long-term challenges on a cancer patient’s health. It is, therefore, highly desirable to develop more effective therapies that can specifically target carcinoma cells without damaging normal and healthy cells. Tremendous efforts have been made in the past to develop targeted drug delivery systems for solid cancer treatment. In this study, a new aptamer, A10-3-J1, which recognizes the extracellular domain of the prostate specific membrane antigen (PSMA), was designed. A super paramagnetic iron oxide nanoparticle-aptamer-doxorubicin (SPIO-Apt-Dox) was fabricated and employed as a targeted drug delivery platform for cancer therapy. This DNA RNA hybridized aptamer antitumor agent was able to enhance the cytotoxicity of targeted cells while minimizing collateral damage to non-targeted cells. This SPIO-Apt-Dox nanoparticle has specificity to PSMA⁺ prostate cancer cells. Aptamer inhibited nonspecific uptake of membrane-permeable doxorubic to the non-target cells, leading to reduced untargeted cytotoxicity and endocytic uptake while enhancing targeted cytotoxicity and endocytic uptake. The experimental results indicate that the drug delivery platform can yield statistically significant effectiveness being more cytotoxic to the targeted cells as opposed to the non-targeted cells. Full article

Open AccessArticle Evaluation of the Cytotoxic Behavior of Fungal Extracellular Synthesized Ag Nanoparticles Using Confocal Laser Scanning Microscope

by Taher A. Salaheldin, Sherif M. Husseiny, Abdullah M. Al-Enizi, Ahmed Elzatahry and Alan H. Cowley

Int. J. Mol. Sci. 2016, 17(3), 329; doi:10.3390/ijms17030329

Received: 20 October 2015 / Revised: 19 February 2016 / Accepted: 19 February 2016 / Published: 3 March 2016

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Abstract

Silver nanoparticles have been synthesized by subjecting a reaction medium to a Fusarium oxysporum biomass at 28 °C for 96 h. The biosynthesized Ag nanoparticles were characterized on the basis of their anticipated peak at 405 nm using UV-Vis-NIR spectroscopy. Structural confirmation was

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Silver nanoparticles have been synthesized by subjecting a reaction medium to a Fusarium oxysporum biomass at 28 °C for 96 h. The biosynthesized Ag nanoparticles were characterized on the basis of their anticipated peak at 405 nm using UV-Vis-NIR spectroscopy. Structural confirmation was evident from the characteristic X-ray diffraction (XRD) pattern, high-resolution transmission electron Microscopy (HRTEM) and the particle size analyzer. The Ag nanoparticles were of dimension 40 ± 5 nm and spherical in shape. The study mainly focused on using the confocal laser scanning microscope (CLSM) to examine the cytotoxic activities of fungal synthesized Ag nanoparticles on a human breast carcinoma cell line MCF7 cell, which featured remarkable vacuolation, thus indicating a potent cytotoxic activity. Full article

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2015

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Open AccessArticle Silica Nanoparticles Induce Oxidative Stress and Autophagy but Not Apoptosis in the MRC-5 Cell Line

by Sorina Nicoleta Petrache Voicu, Diana Dinu, Cornelia Sima, Anca Hermenean, Aurel Ardelean, Elena Codrici, Miruna Silvia Stan, Otilia Zărnescu and Anca Dinischiotu

Int. J. Mol. Sci. 2015, 16(12), 29398-29416; doi:10.3390/ijms161226171

Received: 21 October 2015 / Revised: 27 November 2015 / Accepted: 30 November 2015 / Published: 10 December 2015

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Abstract

This study evaluated the in vitro effects of 62.5 µg/mL silica nanoparticles (SiO₂ NPs) on MRC-5 human lung fibroblast cells for 24, 48 and 72 h. The nanoparticles’ morphology, composition, and structure were investigated using high resolution transmission electron microscopy, selected area

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This study evaluated the in vitro effects of 62.5 µg/mL silica nanoparticles (SiO₂ NPs) on MRC-5 human lung fibroblast cells for 24, 48 and 72 h. The nanoparticles’ morphology, composition, and structure were investigated using high resolution transmission electron microscopy, selected area electron diffraction and X-ray diffraction. Our study showed a decreased cell viability and the induction of cellular oxidative stress as evidenced by an increased level of reactive oxygen species (ROS), carbonyl groups, and advanced oxidation protein products after 24, 48, and 72 h, as well as a decreased concentration of glutathione (GSH) and protein sulfhydryl groups. The protein expression of Hsp27, Hsp60, and Hsp90 decreased at all time intervals, while the level of protein Hsp70 remained unchanged during the exposure. Similarly, the expression of p53, MDM2 and Bcl-2 was significantly decreased for all time intervals, while the expression of Bax, a marker for apoptosis, was insignificantly downregulated. These results correlated with the increase of pro-caspase 3 expression. The role of autophagy in cellular response to SiO₂ NPs was demonstrated by a fluorescence-labeled method and by an increased level of LC3-II/LC3-I ratio. Taken together, our data suggested that SiO₂ NPs induced ROS-mediated autophagy in MRC-5 cells as a possible mechanism of cell survival. Full article

Open AccessArticle Intravenous Administration of Cilostazol Nanoparticles Ameliorates Acute Ischemic Stroke in a Cerebral Ischemia/Reperfusion-Induced Injury Model

by Noriaki Nagai, Chiaki Yoshioka, Yoshimasa Ito, Yoshinori Funakami, Hiroyuki Nishikawa and Atsufumi Kawabata

Int. J. Mol. Sci. 2015, 16(12), 29329-29344; doi:10.3390/ijms161226166

Received: 1 September 2015 / Revised: 30 November 2015 / Accepted: 3 December 2015 / Published: 9 December 2015

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Abstract

It was reported that cilostazol (CLZ) suppressed disruption of the microvasculature in ischemic areas. In this study, we have designed novel injection formulations containing CLZ nanoparticles using 0.5% methylcellulose, 0.2% docusate sodium salt, and mill methods (CLZ_nano dispersion; particle size 81 ±

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It was reported that cilostazol (CLZ) suppressed disruption of the microvasculature in ischemic areas. In this study, we have designed novel injection formulations containing CLZ nanoparticles using 0.5% methylcellulose, 0.2% docusate sodium salt, and mill methods (CLZ_nano dispersion; particle size 81 ± 59 nm, mean ± S.D.), and investigated their toxicity and usefulness in a cerebral ischemia/reperfusion-induced injury model (MCAO/reperfusion mice). The pharmacokinetics of injections of CLZ_nano dispersions is similar to that of CLZ solutions prepared with 2-hydroxypropyl-β-cyclodextrin, and no changes in the rate of hemolysis of rabbit red blood cells, a model of cell injury, were observed with CLZ_nano dispersions. In addition, the intravenous injection of 0.6 mg/kg CLZ_nano dispersions does not affect the blood pressure and blood flow, and the 0.6 mg/kg CLZ_nano dispersions ameliorate neurological deficits and ischemic stroke in MCAO/reperfusion mice. It is possible that the CLZ_nano dispersions will provide effective therapy for ischemic stroke patients, and that injection preparations of lipophilic drugs containing drug nanoparticles expand their therapeutic usage. Full article

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Open AccessArticle Effects of Monotypic and Binary Mixtures of Metal Oxide Nanoparticles on Microbial Growth in Sandy Soil Collected from Artificial Recharge Sites

by Kyung-Seok Ko, Kyoochul Ha and In Chul Kong

Int. J. Mol. Sci. 2015, 16(11), 27967-27977; doi:10.3390/ijms161126066

Received: 23 September 2015 / Revised: 17 November 2015 / Accepted: 17 November 2015 / Published: 24 November 2015

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Abstract

The potential effects of monotypic and binary metal oxide nanoparticles (NPs, ZnO, NiO, Co₃O₄ and TiO₂) on microbial growth were evaluated in sandy soil collected from artificial recharge sites. Microbial growth was assessed based on adenosine triphosphate (ATP)

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The potential effects of monotypic and binary metal oxide nanoparticles (NPs, ZnO, NiO, Co₃O₄ and TiO₂) on microbial growth were evaluated in sandy soil collected from artificial recharge sites. Microbial growth was assessed based on adenosine triphosphate (ATP) content, dehydrogenase activity (DHA), and viable cell counts (VCC). Microbial growth based on ATP content and VCC showed considerable differences depending on NP type and concentration, whereas DHA did not significantly change. In general, ZnO NPs showed the strongest effect on microbial growth in all measurements, showing an EC₅₀ value of 10.9 mg/L for ATP content. The ranking (EC₅₀) of NPs based on their effect on microbial growth assessed by ATP content and VCC was ZnO > Co₃O₄ > NiO > TiO₂. Upon exposure to binary NP mixtures, synergistic and additive modes of action were observed for ATP content and VCC, respectively. The ranges of observed (P(O)) and expected (P(E)) activity were 83%–92% and 78%–82% of the control (p-value 0.0010) based on ATP content and 78%–95% and 72%–94% of the control (p-value 0.8813) based on VCC under the tested conditions, respectively. The results indicate that the effects of NP mixtures on microbial growth in the sandy soil matrix were as great, or greater, than those of single NPs. Therefore, understanding the effects of single NPs and NP mixtures is essential for proper ecological risk assessment. Additionally, these findings demonstrate that the evaluation of NP effects may be profoundly influenced by the method of microbial growth measurement. Full article

Open AccessArticle Safety Profile of TiO₂-Based Photocatalytic Nanofabrics for Indoor Formaldehyde Degradation

by Guixin Cui, Yan Xin, Xin Jiang, Mengqi Dong, Junling Li, Peng Wang, Shumei Zhai, Yongchun Dong, Jianbo Jia and Bing Yan

Int. J. Mol. Sci. 2015, 16(11), 27721-27729; doi:10.3390/ijms161126055

Received: 29 September 2015 / Revised: 2 November 2015 / Accepted: 11 November 2015 / Published: 19 November 2015

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Abstract

Anatase TiO₂ nanoparticles (TNPs) are synthesized using the sol-gel method and loaded onto the surface of polyester-cotton (65/35) fabrics. The nanofabrics degrade formaldehyde at an efficiency of 77% in eight hours with visible light irradiation or 97% with UV light. The loaded

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Anatase TiO₂ nanoparticles (TNPs) are synthesized using the sol-gel method and loaded onto the surface of polyester-cotton (65/35) fabrics. The nanofabrics degrade formaldehyde at an efficiency of 77% in eight hours with visible light irradiation or 97% with UV light. The loaded TNPs display very little release from nanofabrics (~0.0%) during a standard fastness to rubbing test. Assuming TNPs may fall off nanofabrics during their life cycles, we also examine the possible toxicity of TNPs to human cells. We found that up to a concentration of 220 μg/mL, they do not affect viability of human acute monocytic leukemia cell line THP-1 macrophages and human liver and kidney cells. Full article

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Open AccessArticle Pooling and Analysis of Published in Vitro Data: A Proof of Concept Study for the Grouping of Nanoparticles

by Myrtill Simkó, Sonja Tischler and Mats-Olof Mattsson

Int. J. Mol. Sci. 2015, 16(11), 26211-26236; doi:10.3390/ijms161125954

Received: 6 July 2015 / Revised: 23 September 2015 / Accepted: 20 October 2015 / Published: 2 November 2015

Cited by 5 | PDF Full-text (2421 KB) | HTML Full-text | XML Full-text | Supplementary Files

Abstract

The study aim was to test the applicability of pooling of nanomaterials-induced in vitro data for identifying the toxic capacity of specific (SiO₂, TiO₂, ZnO, CuO, CeO₂ and carbon nanotubes, [CNT]) nanoparticles (NP) and to test the usefulness

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The study aim was to test the applicability of pooling of nanomaterials-induced in vitro data for identifying the toxic capacity of specific (SiO₂, TiO₂, ZnO, CuO, CeO₂ and carbon nanotubes, [CNT]) nanoparticles (NP) and to test the usefulness for grouping purposes. Publication selection was based on specific criteria regarding experimental conditions. Two relevant biological endpoints were selected; generation of intracellular reactive oxygen species (ROS) and viability above 90%. The correlations of the ROS ratios with the NP parameters’ size, concentration, and exposure time were analysed. The obtained data sets were then analysed with multiple regression analysis of variance (ANOVA) and the Tukey post-hoc test. The results show that this method is applicable for the selected metal oxide NP, but might need reconsideration and a larger data set for CNT. Several statistically significant correlations and results were obtained, thus validating the method. Furthermore, the relevance of the combination of ROS release with a cell viability test was shown. The data also show that it is advisable to compare ROS production of professional phagocytic with non-phagocytic cells. In conclusion, this is the first systematic analysis showing that pooling of available data into groups is a useful method for evaluation of data regarding NP induced toxicity in vitro. Full article

Open AccessArticle Graphene Functionalized with Arginine Decreases the Development of Glioblastoma Multiforme Tumor in a Gene-Dependent Manner

by Ewa Sawosz, Sławomir Jaworski, Marta Kutwin, Krishna Prasad Vadalasetty, Marta Grodzik, Mateusz Wierzbicki, Natalia Kurantowicz, Barbara Strojny, Anna Hotowy, Ludwika Lipińska, Joanna Jagiełło and André Chwalibog

Int. J. Mol. Sci. 2015, 16(10), 25214-25233; doi:10.3390/ijms161025214

Received: 6 August 2015 / Revised: 2 October 2015 / Accepted: 10 October 2015 / Published: 23 October 2015

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Abstract

Our previous studies revealed that graphene had anticancer properties in experiments in vitro with glioblastoma multiforme (GBM) cells and in tumors cultured in vivo. We hypothesized that the addition of arginine or proline to graphene solutions might counteract graphene agglomeration and increase the

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Our previous studies revealed that graphene had anticancer properties in experiments in vitro with glioblastoma multiforme (GBM) cells and in tumors cultured in vivo. We hypothesized that the addition of arginine or proline to graphene solutions might counteract graphene agglomeration and increase the activity of graphene. Experiments were performed in vitro with GBM U87 cells and in vivo with GBM tumors cultured on chicken embryo chorioallantoic membranes. The measurements included cell morphology, mortality, viability, tumor morphology, histology, and gene expression. The cells and tumors were treated with reduced graphene oxide (rGO) and rGO functionalized with arginine (rGO + Arg) or proline (rGO + Pro). The results confirmed the anticancer effect of graphene on GBM cells and tumor tissue. After functionalization with amino acids, nanoparticles were distributed more specifically, and the flakes of graphene were less agglomerated. The molecule of rGO + Arg did not increase the expression of TP53 in comparison to rGO, but did not increase the expression of MDM2 or the MDM2/TP53 ratio in the tumor, suggesting that arginine may block MDM2 expression. The expression of NQO1, known to be a strong protector of p53 protein in tumor tissue, was greatly increased. The results indicate that the complex of rGO + Arg has potential in GBM therapy. Full article

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Open AccessArticle Structural Analysis of Crystalline R(+)-α-Lipoic Acid-α-cyclodextrin Complex Based on Microscopic and Spectroscopic Studies

by Naoko Ikuta, Takatsugu Endo, Shota Hosomi, Keita Setou, Shiori Tanaka, Noriko Ogawa, Hiromitsu Yamamoto, Tomoyuki Mizukami, Shoji Arai, Masayuki Okuno, Kenji Takahashi, Keiji Terao and Seiichi Matsugo

Int. J. Mol. Sci. 2015, 16(10), 24614-24628; doi:10.3390/ijms161024614

Received: 4 September 2015 / Revised: 5 October 2015 / Accepted: 8 October 2015 / Published: 16 October 2015

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Abstract

R(+)-α-lipoic acid (RALA) is a naturally-occurring substance, and its protein-bound form plays significant role in the energy metabolism in the mitochondria. RALA is vulnerable to a variety of physical stimuli, including heat and UV light, which prompted us to study the stability

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R(+)-α-lipoic acid (RALA) is a naturally-occurring substance, and its protein-bound form plays significant role in the energy metabolism in the mitochondria. RALA is vulnerable to a variety of physical stimuli, including heat and UV light, which prompted us to study the stability of its complexes with cyclodextrins (CDs). In this study, we have prepared and purified a crystalline RALA-αCD complex and evaluated its properties in the solid state. The results of ¹H NMR and PXRD analyses indicated that the crystalline RALA-αCD complex is a channel type complex with a molar ratio of 2:3 (RALA:α-CD). Attenuated total reflection/Fourier transform infrared analysis of the complex showed the shift of the C=O stretching vibration of RALA due to the formation of the RALA-αCD complex. Raman spectroscopic analysis revealed the significant weakness of the S–S and C–S stretching vibrations of RALA in the RALA-αCD complex implying that the dithiolane ring of RALA is almost enclosed in glucose ring of α-CD. Extent of this effect was dependent on the direction of the excitation laser to the hexagonal morphology of the crystal. Solid-state NMR analysis allowed for the chemical shift of the C=O peak to be precisely determined. These results suggested that RALA was positioned in the α-CD cavity with its 1,2-dithiolane ring orientated perpendicular to the plane of the α-CD ring. Full article

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Open AccessArticle Staphylococcus aureus and MRSA Growth and Biofilm Formation after Treatment with Antibiotics and SeNPs

by Kristyna Cihalova, Dagmar Chudobova, Petr Michalek, Amitava Moulick, Roman Guran, Pavel Kopel, Vojtech Adam and Rene Kizek

Int. J. Mol. Sci. 2015, 16(10), 24656-24672; doi:10.3390/ijms161024656

Received: 30 July 2015 / Revised: 3 September 2015 / Accepted: 14 September 2015 / Published: 16 October 2015

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Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a dangerous pathogen resistant to β-lactam antibiotics. Due to its resistance, it is difficult to manage the infections caused by this strain. We examined this issue in terms of observation of the growth properties and ability to form

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Methicillin-resistant Staphylococcus aureus (MRSA) is a dangerous pathogen resistant to β-lactam antibiotics. Due to its resistance, it is difficult to manage the infections caused by this strain. We examined this issue in terms of observation of the growth properties and ability to form biofilms in sensitive S. aureus and MRSA after the application of antibiotics (ATBs)—ampicillin, oxacillin and penicillin—and complexes of selenium nanoparticles (SeNPs) with these ATBs. The results suggest the strong inhibition effect of SeNPs in complexes with conventional ATBs. Using the impedance method, a higher disruption of biofilms was observed after the application of ATB complexes with SeNPs compared to the group exposed to ATBs without SeNPs. The biofilm formation was intensely inhibited (up to 99% ± 7% for S. aureus and up to 94% ± 4% for MRSA) after application of SeNPs in comparison with bacteria without antibacterial compounds whereas ATBs without SeNPs inhibited S. aureus up to 79% ± 5% and MRSA up to 16% ± 2% only. The obtained results provide a basis for the use of SeNPs as a tool for the treatment of bacterial infections, which can be complicated because of increasing resistance of bacteria to conventional ATB drugs. Full article

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Open AccessArticle Liver Toxicity of Cadmium Telluride Quantum Dots (CdTe QDs) Due to Oxidative Stress in Vitro and in Vivo

by Ting Zhang, Yuanyuan Hu, Meng Tang, Lu Kong, Jiali Ying, Tianshu Wu, Yuying Xue and Yuepu Pu

Int. J. Mol. Sci. 2015, 16(10), 23279-23299; doi:10.3390/ijms161023279

Received: 5 August 2015 / Revised: 8 September 2015 / Accepted: 15 September 2015 / Published: 25 September 2015

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Abstract

With the applications of quantum dots (QDs) expanding, many studies have described the potential adverse effects of QDs, yet little attention has been paid to potential toxicity of QDs in the liver. The aim of this study was to investigate the effects of

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With the applications of quantum dots (QDs) expanding, many studies have described the potential adverse effects of QDs, yet little attention has been paid to potential toxicity of QDs in the liver. The aim of this study was to investigate the effects of cadmium telluride (CdTe) QDs in mice and murine hepatoma cells alpha mouse liver 12 (AML 12). CdTe QDs administration significantly increased the level of lipid peroxides marker malondialdehyde (MDA) in the livers of treated mice. Furthermore, CdTe QDs caused cytotoxicity in AML 12 cells in a dose- and time-dependent manner, which was likely mediated through the generation of reactive oxygen species (ROS) and the induction of apoptosis. An increase in ROS generation with a concomitant increase in the gene expression of the tumor suppressor gene p53, the pro-apoptotic gene Bcl-2 and a decrease in the anti-apoptosis gene Bax, suggested that a mitochondria mediated pathway was involved in CdTe QDs’ induced apoptosis. Finally, we showed that NF-E2-related factor 2 (Nrf2) deficiency blocked induced oxidative stress to protect cells from injury induced by CdTe QDs. These findings provide insights into the regulatory mechanisms involved in the activation of Nrf2 signaling that confers protection against CdTe QDs-induced apoptosis in hepatocytes. Full article

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Open AccessArticle Attenuation of Combined Nickel(II) Oxide and Manganese(II, III) Oxide Nanoparticles’ Adverse Effects with a Complex of Bioprotectors

by Ilzira A. Minigalieva, Boris A. Katsnelson, Larisa I. Privalova, Marina P. Sutunkova, Vladimir B. Gurvich, Vladimir Y. Shur, Ekaterina V. Shishkina, Irene E. Valamina, Oleg H. Makeyev, Vladimir G. Panov, Anatoly N. Varaksin, Ekaterina V. Grigoryeva and Ekaterina Y. Meshtcheryakova

Int. J. Mol. Sci. 2015, 16(9), 22555-22583; doi:10.3390/ijms160922555

Received: 14 August 2015 / Revised: 7 September 2015 / Accepted: 8 September 2015 / Published: 17 September 2015

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Abstract

Stable suspensions of NiO and Mn₃O₄ nanoparticles (NPs) with a mean (±s.d.) diameter of 16.7 ± 8.2 and 18.4 ± 5.4 nm, respectively, purposefully prepared by laser ablation of 99.99% pure nickel or manganese in de-ionized water, were repeatedly injected

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Stable suspensions of NiO and Mn₃O₄ nanoparticles (NPs) with a mean (±s.d.) diameter of 16.7 ± 8.2 and 18.4 ± 5.4 nm, respectively, purposefully prepared by laser ablation of 99.99% pure nickel or manganese in de-ionized water, were repeatedly injected intraperitoneally (IP) to rats at a dose of 2.5 mg/kg 3 times a week up to 18 injections, either alone or in combination. A group of rats was injected with this combination with the background oral administration of a “bio-protective complex” (BPC) comprising pectin, vitamins A, C, E, glutamate, glycine, N-acetylcysteine, selenium, iodide and omega-3 PUFA, this composition having been chosen based on mechanistic considerations and previous experience. After the termination of injections, many functional and biochemical indices and histopathological features (with morphometric assessment) of the liver, spleen, kidneys and brain were evaluated for signs of toxicity. The Ni and Mn content of these organs was measured with the help of the atomic emission and electron paramagnetic resonance spectroscopies. We obtained blood leukocytes for performing the RAPD (Random Amplified Polymorphic DNA) test. Although both metallic NPs proved adversely bio-active in many respects considered in this study, Mn₃O₄-NPswere somewhat more noxious than NiO-NPs as concerns most of the non-specific toxicity manifestations and they induced more marked damage to neurons in the striatum and the hippocampus, which may be considered an experimental correlate of the manganese-induced Parkinsonism. The comparative solubility of the Mn₃O₄-NPs and NiO-NPs in a biological medium is discussed as one of the factors underlying the difference in their toxicokinetics and toxicities. The BPC has attenuated both the organ-systemic toxicity and the genotoxicity of Mn₃O₄-NPs in combination with NiO-NPs. Full article

Open AccessArticle Influence of Parathyroid Hormone-Loaded PLGA Nanoparticles in Porous Scaffolds for Bone Regeneration

by Piergiorgio Gentile, Vijay Kumar Nandagiri, Ritesh Pabari, Jacqueline Daly, Chiara Tonda-Turo, Gianluca Ciardelli and Zebunnissa Ramtoola

Int. J. Mol. Sci. 2015, 16(9), 20492-20510; doi:10.3390/ijms160920492

Received: 21 July 2015 / Revised: 5 August 2015 / Accepted: 7 August 2015 / Published: 28 August 2015

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Abstract

Biodegradable poly(lactide-co-glycolide) (PLGA) nanoparticles, containing human parathyroid hormone (PTH (1–34)), prepared by a modified double emulsion-solvent diffusion-evaporation method, were incorporated in porous freeze-dried chitosan-gelatin (CH-G) scaffolds. The PTH-loaded nanoparticles (NPTH) were characterised in terms of morphology, size, protein loading, release kinetics

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Biodegradable poly(lactide-co-glycolide) (PLGA) nanoparticles, containing human parathyroid hormone (PTH (1–34)), prepared by a modified double emulsion-solvent diffusion-evaporation method, were incorporated in porous freeze-dried chitosan-gelatin (CH-G) scaffolds. The PTH-loaded nanoparticles (NPTH) were characterised in terms of morphology, size, protein loading, release kinetics and in vitro assessment of biological activity of released PTH and cytocompatibility studies against clonal human osteoblast (hFOB) cells. Structural integrity of incorporated and released PTH from nanoparticles was found to be intact by using Tris-tricine SDS-PAGE. In vitro PTH release kinetics from PLGA nanoparticles were characterised by a burst release followed by a slow release phase for 3–4 weeks. The released PTH was biologically active as evidenced by the stimulated release of cyclic AMP from hFOB cells as well as increased mineralisation studies. in vitro and cell studies demonstrated that the PTH bioactivity was maintained during the fabrication of PLGA nanoparticles and upon release. Finally, a content of 33.3% w/w NPTHs was incorporated in CH-G scaffolds, showing an intermittent release during the first 10 days and, followed by a controlled release over 28 days of observation time. The increased expression of Alkaline Phosphatase levels on hFOB cells further confirmed the activity of intermittently released PTH from scaffolds. Full article

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Open AccessArticle New Hybrid Nanomaterial Based on Self-Assembly of Cyclodextrins and Cobalt Prussian Blue Analogue Nanocubes

by Caio L. C. Carvalho, Anna T. B. Silva, Lucyano J. A. Macedo, Roberto A. S. Luz, José M. Moita Neto, Ubirajara P. Rodrigues Filho and Welter Cantanhêde

Int. J. Mol. Sci. 2015, 16(7), 14594-14607; doi:10.3390/ijms160714594

Received: 27 February 2015 / Revised: 31 March 2015 / Accepted: 8 April 2015 / Published: 29 June 2015

Cited by 2 | PDF Full-text (1218 KB) | HTML Full-text | XML Full-text | Supplementary Files

Abstract

Supramolecular self-assembly has been demonstrated to be a useful approach to developing new functional nanomaterials. In this work, we used a cobalt Prussian blue analogue (PBA, Co₃[Co(CN)₆]₂) compound and a β-cyclodextrin (CD) macrocycle to develop a novel

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Supramolecular self-assembly has been demonstrated to be a useful approach to developing new functional nanomaterials. In this work, we used a cobalt Prussian blue analogue (PBA, Co₃[Co(CN)₆]₂) compound and a β-cyclodextrin (CD) macrocycle to develop a novel host-guest PBA-CD nanomaterial. The preparation of the functional magnetic material involved the self-assembly of CD molecules onto a PBA surface by a co-precipitation method. According to transmission electronic microscopy results, PBA-CD exhibited a polydisperse structure composed of 3D nanocubes with a mean edge length of 85 nm, which became shorter after CD incorporation. The supramolecular arrangement and structural, crystalline and thermal properties of the hybrid material were studied in detail by vibrational and electronic spectroscopies and X-ray diffraction. The cyclic voltammogram of the hybrid material in a 0.1 mol·L⁻¹ NaCl supporting electrolyte exhibited a quasi-reversible redox process, attributed to Co²⁺/Co³⁺ conversion, with an E_1/2 value of 0.46 V (vs. SCE), with higher reversibility observed for the system in the presence of CD. The standard rate constants for PBA and PBA-CD were determined to be 0.07 and 0.13 s⁻¹, respectively, which suggests that the interaction between the nanocubes and CD at the supramolecular level improves electron transfer. We expect that the properties observed for the hybrid material make it a potential candidate for (bio)sensing designs with a desirable capability for drug delivery. Full article

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Open AccessArticle Microwave-Assisted Synthesis of Glutathione-Capped CdTe/CdSe Near-Infrared Quantum Dots for Cell Imaging

by Xiaogang Chen, Liang Li, Yongxian Lai, Jianna Yan, Yichen Tang and Xiuli Wang

Int. J. Mol. Sci. 2015, 16(5), 11500-11508; doi:10.3390/ijms160511500

Received: 10 March 2015 / Revised: 11 May 2015 / Accepted: 11 May 2015 / Published: 19 May 2015

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Abstract

These glutathione (GSH)-conjugated CdTe/CdSe core/shell quantum dot (QD) nanoparticles in aqueous solution were synthesized using a microwave-assisted approach. The prepared type II core/shell QD nanoparticles were characterized by UV–Vis absorption, photoluminescence (PL) spectroscopy, X-ray powder diffraction (XRD) and high-resolution transmission electron microscopy (HR-TEM).

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These glutathione (GSH)-conjugated CdTe/CdSe core/shell quantum dot (QD) nanoparticles in aqueous solution were synthesized using a microwave-assisted approach. The prepared type II core/shell QD nanoparticles were characterized by UV–Vis absorption, photoluminescence (PL) spectroscopy, X-ray powder diffraction (XRD) and high-resolution transmission electron microscopy (HR-TEM). Results revealed that the QD nanoparticles exhibited good dispersity, a uniform size distribution and tunable fluorescence emission in the near-infrared (NIR) region. In addition, these nanoparticles exhibited good biocompatibility and photoluminescence in cell imaging. In particular, this type of core/shell NIR QDs may have potential applications in molecular imaging. Full article

Open AccessArticle In Ovo Administration of Silver Nanoparticles and/or Amino Acids Influence Metabolism and Immune Gene Expression in Chicken Embryos

by Subrat K. Bhanja, Anna Hotowy, Manish Mehra, Ewa Sawosz, Lane Pineda, Krishna Prasad Vadalasetty, Natalia Kurantowicz and André Chwalibog

Int. J. Mol. Sci. 2015, 16(5), 9484-9503; doi:10.3390/ijms16059484

Received: 15 March 2015 / Revised: 17 April 2015 / Accepted: 21 April 2015 / Published: 27 April 2015

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Abstract

Due to their physicochemical and biological properties, silver nanoparticles (NanoAg) have a wide range of applications. In the present study, their roles as a carrier of nutrients and an immunomodulator were tested in chicken embryos. Cysteine (Cys)+NanoAg injected embryos had smaller livers but

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Due to their physicochemical and biological properties, silver nanoparticles (NanoAg) have a wide range of applications. In the present study, their roles as a carrier of nutrients and an immunomodulator were tested in chicken embryos. Cysteine (Cys)+NanoAg injected embryos had smaller livers but heavier breasts on the 19th day of embryogenesis. Cys injected embryos had lower oxygen consumption compared to threonine (Thr) or NanoAg injected embryos. The energy expenditure in Thr+NanoAg, or NanoAg injected embryos was higher than Cys or Cys+NanoAg but was not different from uninjected control embryos. Relative expression of the hepatic insulin-like growth factor-I (IGF-I) gene was higher in Cys or NanoAg injected embryos after lipopolysaccharide (LPS) induction. The gene expression of hepatic tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) did not differ among amino acids, NanoAg and uninjected controls in the non-LPS groups, but increased by many folds in the LPS treated NanoAg, Cys and Cys+NanoAg groups. In LPS treated spleens, TNF-α expression was also up-regulated by NanoAg, amino acids and their combinations, but interleukin-10 (IL-10) expression was down-regulated in Thr, Cys or Thr+NanoAg injected embryos. Toll like receptor-2 (TLR2) expression did not differ in NanoAg or amino acids injected embryos; however, toll like receptor-4 (TLR4) expression was higher in all treated embryos, except for Cys+NanoAg, than in uninjected control embryos. We concluded that NanoAg either alone or in combination with amino acids did not affect embryonic growth but improved immunocompetence, indicating that NanoAg and amino acid complexes can act as potential agents for the enhancement of innate and adaptive immunity in chicken. Full article

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Open AccessArticle In Vitro Cytotoxic Evaluation of MgO Nanoparticles and Their Effect on the Expression of ROS Genes

by Rangarajulu Senthil Kumaran, Yong-Keun Choi, Vijay Singh, Hak-Jin Song, Kyung-Guen Song, Kwang Jin Kim and Hyung Joo Kim

Int. J. Mol. Sci. 2015, 16(4), 7551-7564; doi:10.3390/ijms16047551

Received: 10 February 2015 / Revised: 19 March 2015 / Accepted: 30 March 2015 / Published: 3 April 2015

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Abstract

Water-dispersible MgO nanoparticles were tested to investigate their cytotoxic effects on oxidative stress gene expression. In this in vitro study, genes related to reactive oxygen species (ROS), glutathione S-transferase (GST) and catalase, were quantified using real-time polymerase chain reactions (molecular level) and

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Water-dispersible MgO nanoparticles were tested to investigate their cytotoxic effects on oxidative stress gene expression. In this in vitro study, genes related to reactive oxygen species (ROS), glutathione S-transferase (GST) and catalase, were quantified using real-time polymerase chain reactions (molecular level) and molecular beacon technologies (cellular level). The monodispersed MgO nanoparticles, 20 nm in size, were used to treat human cancer cell lines (liver cancer epithelial cells) at different concentrations (25, 75 and 150 µg/mL) and incubation times (24, 48 and 72 h). Both the genetic and cellular cytotoxic screening methods produced consistent results, showing that GST and catalase ROS gene expression was maximized at 150 µg/mL nanoparticle treatment with 48 h incubation. However, the genotoxic effect of MgO nanoparticles was not significant compared with control experiments, which indicates its significant potential applications in nanomedicine as a diagnostic and therapeutic tool. Full article

Open AccessArticle In Vitro Investigation of Self-Assembled Nanoparticles Based on Hyaluronic Acid-Deoxycholic Acid Conjugates for Controlled Release Doxorubicin: Effect of Degree of Substitution of Deoxycholic Acid

by Wen-Hao Wei, Xue-Meng Dong and Chen-Guang Liu

Int. J. Mol. Sci. 2015, 16(4), 7195-7209; doi:10.3390/ijms16047195

Received: 22 September 2014 / Revised: 6 January 2015 / Accepted: 22 January 2015 / Published: 31 March 2015

Cited by 5 | PDF Full-text (795 KB) | HTML Full-text | XML Full-text

Abstract

Self-assembled nanoparticles based on a hyaluronic acid-deoxycholic acid (HD) chemical conjugate with different degree of substitution (DS) of deoxycholic acid (DOCA) were prepared. The degree of substitution (DS) was determined by titration method. The nanoparticles were loaded with doxorubicin (DOX) as the model

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Self-assembled nanoparticles based on a hyaluronic acid-deoxycholic acid (HD) chemical conjugate with different degree of substitution (DS) of deoxycholic acid (DOCA) were prepared. The degree of substitution (DS) was determined by titration method. The nanoparticles were loaded with doxorubicin (DOX) as the model drug. The human cervical cancer (HeLa) cell line was utilized for in vitro studies and cell cytotoxicity of DOX incorporated in the HD nanoparticles was accessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, cellular uptake of fluorescently labeled nanoparticles was also investigated. An increase in the degree of deoxycholic acid substitution reduced the size of the nanoparticles and also enhanced their drug encapsulation efficiency (EE), which increased with the increase of DS. A higher degree of deoxycholic acid substitution also lead to a lower release rate and an initial burst release of doxorubicin from the nanoparticles. In summary, the degree of substitution allows the modulation of the particle size, drug encapsulation efficiency, drug release rate, and cell uptake efficiency of the nanoparticles. The herein developed hyaluronic acid-deoxycholic acid conjugates are a good candidate for drug delivery and could potentiate therapeutic formulations for doxorubicin–mediated cancer therapy. Full article

Open AccessArticle Tumour Cell Membrane Poration and Ablation by Pulsed Low-Intensity Electric Field with Carbon Nanotubes

by Lijun Wang, Dun Liu, Ru Zhou, Zhigang Wang and Alfred Cuschieri

Int. J. Mol. Sci. 2015, 16(4), 6890-6901; doi:10.3390/ijms16046890

Received: 3 February 2015 / Revised: 19 March 2015 / Accepted: 23 March 2015 / Published: 26 March 2015

Cited by 3 | PDF Full-text (1393 KB) | HTML Full-text | XML Full-text

Abstract

Electroporation is a physical method to increase permeabilization of cell membrane by electrical pulses. Carbon nanotubes (CNTs) can potentially act like “lighting rods” or exhibit direct physical force on cell membrane under alternating electromagnetic fields thus reducing the required field strength. A cell

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Electroporation is a physical method to increase permeabilization of cell membrane by electrical pulses. Carbon nanotubes (CNTs) can potentially act like “lighting rods” or exhibit direct physical force on cell membrane under alternating electromagnetic fields thus reducing the required field strength. A cell poration/ablation system was built for exploring these effects of CNTs in which two-electrode sets were constructed and two perpendicular electric fields could be generated sequentially. By applying this system to breast cancer cells in the presence of multi-walled CNTs (MWCNTs), the effective pulse amplitude was reduced to 50 V/cm (main field)/15 V/cm (alignment field) at the optimized pulse frequency (5 Hz) of 500 pulses. Under these conditions instant cell membrane permeabilization was increased to 38.62%, 2.77-fold higher than that without CNTs. Moreover, we also observed irreversible electroporation occurred under these conditions, such that only 39.23% of the cells were viable 24 h post treatment, in contrast to 87.01% cell viability without presence of CNTs. These results indicate that CNT-enhanced electroporation has the potential for tumour cell ablation by significantly lower electric fields than that in conventional electroporation therapy thus avoiding potential risks associated with the use of high intensity electric pulses. Full article

Open AccessReview Silk Fibroin-Based Nanoparticles for Drug Delivery

by Zheng Zhao, Yi Li and Mao-Bin Xie

Int. J. Mol. Sci. 2015, 16(3), 4880-4903; doi:10.3390/ijms16034880

Received: 17 November 2014 / Revised: 1 February 2015 / Accepted: 2 February 2015 / Published: 4 March 2015

Cited by 30 | PDF Full-text (1425 KB) | HTML Full-text | XML Full-text

Abstract

Silk fibroin (SF) is a protein-based biomacromolecule with excellent biocompatibility, biodegradability and low immunogenicity. The development of SF-based nanoparticles for drug delivery have received considerable attention due to high binding capacity for various drugs, controlled drug release properties and mild preparation conditions. By

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Silk fibroin (SF) is a protein-based biomacromolecule with excellent biocompatibility, biodegradability and low immunogenicity. The development of SF-based nanoparticles for drug delivery have received considerable attention due to high binding capacity for various drugs, controlled drug release properties and mild preparation conditions. By adjusting the particle size, the chemical structure and properties, the modified or recombinant SF-based nanoparticles can be designed to improve the therapeutic efficiency of drugs encapsulated into these nanoparticles. Therefore, they can be used to deliver small molecule drugs (e.g., anti-cancer drugs), protein and growth factor drugs, gene drugs, etc. This paper reviews recent progress on SF-based nanoparticles, including chemical structure, properties, and preparation methods. In addition, the applications of SF-based nanoparticles as carriers for therapeutic drugs are also reviewed. Full article

Open AccessArticle Nanoparticles of Copper Stimulate Angiogenesis at Systemic and Molecular Level

by Natalia Mroczek-Sosnowska, Ewa Sawosz, Krishna Prasad Vadalasetty, Monika Łukasiewicz, Jan Niemiec, Mateusz Wierzbicki, Marta Kutwin, Sławomir Jaworski and André Chwalibog

Int. J. Mol. Sci. 2015, 16(3), 4838-4849; doi:10.3390/ijms16034838

Received: 19 January 2015 / Revised: 12 February 2015 / Accepted: 15 February 2015 / Published: 3 March 2015

Cited by 18 | PDF Full-text (2972 KB) | HTML Full-text | XML Full-text

Abstract

Copper is a key element affecting blood vessel growth and muscle development. However, the ions released from Cu salts are toxic. Given their specific physicochemical properties, nanoparticles of Cu (NanoCu) may have different bioactivity and affect the development of blood vessel and muscles

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Copper is a key element affecting blood vessel growth and muscle development. However, the ions released from Cu salts are toxic. Given their specific physicochemical properties, nanoparticles of Cu (NanoCu) may have different bioactivity and affect the development of blood vessel and muscles in a different manner than Cu salts. The objective of the study was to evaluate the influence of NanoCu on embryo development and angiogenesis at the systemic and molecular level, in experiments using a chick embryo model. Fertilized chicken eggs were divided into a control group, and groups injected with a placebo, CuSO₄ or NanoCu. Embryo development at the whole body level and molecular indices using an embryo chorioallantoic membrane model were measured during embryogenesis. The present study indicated for the first time that NanoCu have pro-angiogenic properties at the systemic level, to a greater degree than CuSO₄ salt. The properties of NanoCu were confirmed at the molecular level, demonstrating significant effects on mRNA concentration and on mRNA gene expression of all pro-angiogenic and pro-proliferative genes measured herein. Full article

Open AccessCommunication Development of Biodegradable Nanocarriers Loaded with a Monoclonal Antibody

by Andrew Gdowski, Amalendu Ranjan, Anindita Mukerjee and Jamboor Vishwanatha

Int. J. Mol. Sci. 2015, 16(2), 3990-3995; doi:10.3390/ijms16023990

Received: 23 December 2014 / Revised: 21 January 2015 / Accepted: 28 January 2015 / Published: 12 February 2015

Cited by 6 | PDF Full-text (983 KB) | HTML Full-text | XML Full-text

Abstract

Treatments utilizing monoclonal antibody therapeutics against intracellular protein-protein interactions in cancer cells have been hampered by several factors, including poor intracellular uptake and rapid lysosomal degradation. Our current work examines the feasibility of encapsulating monoclonal antibodies within poly(lactic-co-glycolic acid) (PLGA) nanoparticles

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Treatments utilizing monoclonal antibody therapeutics against intracellular protein-protein interactions in cancer cells have been hampered by several factors, including poor intracellular uptake and rapid lysosomal degradation. Our current work examines the feasibility of encapsulating monoclonal antibodies within poly(lactic-co-glycolic acid) (PLGA) nanoparticles using a water/oil/water double emulsion solvent evaporation technique. This method can be used to prepare protective polymeric nanoparticles for transporting functional antibodies to the cytoplasmic compartment of cancer cells. Nanoparticles were formulated and then characterized using a number of physical and biological parameters. The average nanoparticle size ranged from 221 to 252 nm with a low polydispersity index. Encapsulation efficiency of 16%–22% and antibody loading of 0.3%–1.12% were observed. The antibody molecules were released from the nanoparticles in a sustained manner and upon release maintained functionality. Our studies achieved successful formulation of antibody loaded polymeric nanoparticles, thus indicating that a PLGA-based antibody nanoformulation is a promising intracellular delivery vehicle for a large number of new intracellular antibody targets in cancer cells. Full article

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Open AccessArticle Multi-Walled Carbon Nanotubes Promote Cementoblast Differentiation and Mineralization through the TGF-β/Smad Signaling Pathway

by Lu Li, Zhimin Zhu, Weixiong Xiao and Lei Li

Int. J. Mol. Sci. 2015, 16(2), 3188-3201; doi:10.3390/ijms16023188

Received: 20 November 2014 / Revised: 19 January 2015 / Accepted: 26 January 2015 / Published: 2 February 2015

Cited by 5 | PDF Full-text (2561 KB) | HTML Full-text | XML Full-text

Abstract

Excretion of cementum by cementoblasts on the root surface is a process indispensable for the formation of a functional periodontal ligament. This study investigated whether carboxyl group-functionalized multi-walled carbon nanotubes (MWCNT-COOH) could enhance differentiation and mineralization of mammalian cementoblasts (OCCM-30) and the possible

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Excretion of cementum by cementoblasts on the root surface is a process indispensable for the formation of a functional periodontal ligament. This study investigated whether carboxyl group-functionalized multi-walled carbon nanotubes (MWCNT-COOH) could enhance differentiation and mineralization of mammalian cementoblasts (OCCM-30) and the possible signaling pathway involved in this process. Cementoblasts were incubated with various doses of MWCNT-COOH suspension. Cell viability was detected, and a scanning electron microscopy (SEM) observed both the nanomaterials and the growth of cells cultured with the materials. Alizarin red staining was used to investigate the formation of calcium deposits. Real-time PCR and western blot were used to detect cementoblast differentiation and the underlying mechanisms through the expression of the osteogenic genes and the downstream effectors of the TGF-β/Smad signaling. The results showed that 5 µg/mL MWCNT-COOH had the most obvious effects on promoting differentiation without significant toxicity. Alp, Ocn, Bsp, Opn, Col1 and Runx2 gene expression was up-regulated. Smad2 and Smad3 mRNA was up-regulated, while Smad7 was first down-regulated on Day 3 and later up-regulated on Day 7. The elevated levels of phospho-Smad2/3 were also confirmed by western blot. In sum, the MWCNT-COOH promoted cementoblast differentiation and mineralization, at least partially, through interactions with the TGF-β/Smad pathway. Full article

Open AccessArticle Efficient Synthesis of a Maghemite/Gold Hybrid Nanoparticle System as a Magnetic Carrier for the Transport of Platinum-Based Metallotherapeutics

by Pavel Štarha, David Smola, Jiří Tuček and Zdeněk Trávníček

Int. J. Mol. Sci. 2015, 16(1), 2034-2051; doi:10.3390/ijms16012034

Received: 11 December 2014 / Accepted: 13 January 2015 / Published: 16 January 2015

Cited by 4 | PDF Full-text (1996 KB) | HTML Full-text | XML Full-text

Abstract

The preparation and thorough characterization of a hybrid magnetic carrier system for the possible transport of activated platinum-based anticancer drugs, as demonstrated for cisplatin (cis-[Pt(NH₃)₂Cl₂], CDDP), are described. The final functionalized mag/Au–LA–CDDP* system consists of

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The preparation and thorough characterization of a hybrid magnetic carrier system for the possible transport of activated platinum-based anticancer drugs, as demonstrated for cisplatin (cis-[Pt(NH₃)₂Cl₂], CDDP), are described. The final functionalized mag/Au–LA–CDDP* system consists of maghemite/gold nanoparticles (mag/Au) coated by lipoic acid (HLA; LA stands for deprotonated form of lipoic acid) and functionalized by activated cisplatin in the form of cis-[Pt(NH₃)₂(H₂O)₂]²⁺ (CDDP*). The relevant techniques (XPS, EDS, ICP-MS) proved the incorporation of the platinum-containing species on the surface of the studied hybrid system. HRTEM, TEM and SEM images showed the nanoparticles as spherical with an average size of 12 nm, while their superparamagnetic feature was proven by ⁵⁷Fe Mössbauer spectroscopy. In the case of mag/Au, mag/Au–HLA and mag/Au–LA–CDDP*, weaker magnetic interactions among the Fe³⁺ centers of maghemite, as compared to maghemite nanoparticles (mag), were detected, which can be associated with the non-covalent coating of the maghemite surface by gold. The pH and time-dependent stability of the mag/Au–LA–CDDP* system in different media, represented by acetate (pH 5.0), phosphate (pH 7.0) and carbonate (pH 9.0) buffers and connected with the release of the platinum-containing species, showed the ability of CDDP* to be released from the functionalized nanosystem. Full article

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Open AccessReview Mechanisms and Implications of Dual-Acting Methotrexate in Folate-Targeted Nanotherapeutic Delivery

by Pamela T. Wong and Seok Ki Choi

Int. J. Mol. Sci. 2015, 16(1), 1772-1790; doi:10.3390/ijms16011772

Received: 23 December 2014 / Accepted: 5 January 2015 / Published: 13 January 2015

Cited by 9 | PDF Full-text (1916 KB) | HTML Full-text | XML Full-text

Abstract

The rational design of a nanoplatform in drug delivery plays a crucial role in determining its targeting specificity and efficacy in vivo. A conventional approach relies on the surface conjugation of a nanometer-sized particle with two functionally distinct types of molecules, one

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The rational design of a nanoplatform in drug delivery plays a crucial role in determining its targeting specificity and efficacy in vivo. A conventional approach relies on the surface conjugation of a nanometer-sized particle with two functionally distinct types of molecules, one as a targeting ligand, and the other as a therapeutic agent to be delivered to the diseased cell. However, an alternative simplified approach can be used, in which a single type of molecule displaying dual function as both a targeting ligand and therapeutic agent is conjugated to the nanoparticle. In this review, we evaluate the validity of this new strategy by using methotrexate, which displays multifunctional mechanisms of action. Methotrexate binds to the folate receptor, a surface biomarker frequently overexpressed in tumor cells, and also inhibits dihydrofolate reductase, an enzyme critical for cell survival and division. Thus we describe a series of fifth generation poly(amido amine) dendrimers conjugated with methotrexate, and discuss several lines of evidence supporting the efficacy of this new platform strategy based on surface plasmon resonance spectroscopy, enzyme activity assays, and cell-based studies with folate receptor (+) KB cancer cells. Full article

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Open AccessArticle Pulicaria glutinosa Extract: A Toolbox to Synthesize Highly Reduced Graphene Oxide-Silver Nanocomposites

by Abdulhadi H. Al-Marri, Mujeeb Khan, Merajuddin Khan, Syed F. Adil, Abdulrahman Al-Warthan, Hamad Z. Alkhathlan, Wolfgang Tremel, Joselito P. Labis, Mohammed Rafiq H. Siddiqui and Muhammad N. Tahir

Int. J. Mol. Sci. 2015, 16(1), 1131-1142; doi:10.3390/ijms16011131

Received: 11 December 2014 / Accepted: 29 December 2014 / Published: 5 January 2015

Cited by 14 | PDF Full-text (1855 KB) | HTML Full-text | XML Full-text

Abstract

A green, one-step approach for the preparation of graphene/Ag nanocomposites (PE-HRG-Ag) via simultaneous reduction of both graphene oxide (GRO) and silver ions using Pulicaria glutinosa plant extract (PE) as reducing agent is reported. The plant extract functionalizes the surfaces of highly reduced graphene

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A green, one-step approach for the preparation of graphene/Ag nanocomposites (PE-HRG-Ag) via simultaneous reduction of both graphene oxide (GRO) and silver ions using Pulicaria glutinosa plant extract (PE) as reducing agent is reported. The plant extract functionalizes the surfaces of highly reduced graphene oxide (HRG) which helps in conjugating the Ag NPs to HRG. Increasing amounts of Ag precursor enhanced the density of Ag nanoparticles (NPs) on HRG. The preparation of PE-HRG-Ag nanocomposite is monitored by using ultraviolet–visible (UV-Vis) spectroscopy, powder X-ray diffraction (XRD), and energy dispersive X-ray (EDX). The as-prepared PE-HRG-Ag nanocomposities display excellent surface-enhanced Raman scattering (SERS) activity, and significantly increased the intensities of the Raman signal of graphene. Full article

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Open AccessArticle Development and Application of a Label-Free Fluorescence Method for Determining the Composition of Gold Nanoparticle–Protein Conjugates

by Dmitriy V. Sotnikov, Anatoly V. Zherdev and Boris B. Dzantiev

Int. J. Mol. Sci. 2015, 16(1), 907-923; doi:10.3390/ijms16010907

Received: 2 December 2014 / Accepted: 18 December 2014 / Published: 31 December 2014

Cited by 5 | PDF Full-text (2747 KB) | HTML Full-text | XML Full-text | Supplementary Files

Abstract

A method was developed for determining the composition of the conjugates between gold nanoparticles and proteins based on the intrinsic fluorescence of unbound protein molecules. The fluorescence was evaluated after separation of the conjugates from the reaction mixture by centrifugation. Gold nanoparticles obtained

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A method was developed for determining the composition of the conjugates between gold nanoparticles and proteins based on the intrinsic fluorescence of unbound protein molecules. The fluorescence was evaluated after separation of the conjugates from the reaction mixture by centrifugation. Gold nanoparticles obtained using the citrate technique (average diameter 24 nm) were conjugated at pH 5.4 with the following four proteins: human immunoglobulin G (IgG), bovine serum albumin (BSA), recombinant streptococcal protein G (protein G), and Kunitz-type soybean trypsin inhibitor (STI). The compositions of these conjugates were determined using the developed method. The conjugate compositions were dependent on the concentration of the added protein, and in all cases reached saturation. The equilibrium dissociation constants of the gold nanoparticle conjugates with IgG, BSA, protein G, STI in the initial section of the concentration dependence curve were 4, 6, 10, and 15 nM, respectively. Close to saturation, the corresponding values were 25, 76, 175, and 100 nM, respectively. The maximal binding capacities of a single gold nanoparticle for IgG, BSA, Protein G, and STI were 52, 90, 500, and 550, respectively, which agrees well with the hypothesis of monolayer immobilization. Full article

Open AccessArticle Synergistic Effect of Bolus Exposure to Zinc Oxide Nanoparticles on Bleomycin-Induced Secretion of Pro-Fibrotic Cytokines without Lasting Fibrotic Changes in Murine Lungs

by Wenting Wu, Gaku Ichihara, Naozumi Hashimoto, Yoshinori Hasegawa, Yasuhiko Hayashi, Saeko Tada-Oikawa, Yuka Suzuki, Jie Chang, Masashi Kato, Corina N. D'Alessandro-Gabazza, Esteban C. Gabazza and Sahoko Ichihara

Int. J. Mol. Sci. 2015, 16(1), 660-676; doi:10.3390/ijms16010660

Received: 16 September 2014 / Accepted: 16 December 2014 / Published: 30 December 2014

Cited by 4 | PDF Full-text (2290 KB) | HTML Full-text | XML Full-text | Supplementary Files

Abstract

Zinc oxide (ZnO) nanoparticles are widely used in various products, and the safety evaluation of this manufactured material is important. The present study investigated the inflammatory and fibrotic effects of pulmonary exposure to ZnO nanoparticles in a mouse model of pulmonary fibrosis. Pulmonary

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Zinc oxide (ZnO) nanoparticles are widely used in various products, and the safety evaluation of this manufactured material is important. The present study investigated the inflammatory and fibrotic effects of pulmonary exposure to ZnO nanoparticles in a mouse model of pulmonary fibrosis. Pulmonary fibrosis was induced by constant subcutaneous infusion of bleomycin (BLM). Female C57BL/6Jcl mice were divided into BLM-treated and non-treated groups. In each treatment group, 0, 10, 20 or 30 µg of ZnO nanoparticles were delivered into the lungs through pharyngeal aspiration. Bronchoalveolar lavage fluid (BALF) and the lungs were sampled at Day 10 or 14 after administration. Pulmonary exposure by a single bolus of ZnO nanoparticles resulted in severe, but transient inflammatory infiltration and thickening of the alveolar septa in the lungs, along with the increase of total and differential cell counts in BLAF. The BALF level of interleukin (IL)-1β and transforming growth factor (TGF)-β was increased at Day 10 and 14, respectively. At Day 10, the synergistic effect of BLM and ZnO exposure was detected on IL-1β and monocyte chemotactic protein (MCP)-1 in BALF. The present study demonstrated the synergistic effect of pulmonary exposure to ZnO nanoparticles and subcutaneous infusion of BLM on the secretion of pro-fibrotic cytokines in the lungs. Full article

Open AccessArticle Systemic Delivery of Protein Nanocages Bearing CTT Peptides for Enhanced Imaging of MMP-2 Expression in Metastatic Tumor Models

by Takahito Kawano, Masaharu Murata, Jing Shu Piao, Sayoko Narahara, Nobuhito Hamano, Jeong-Hun Kang and Makoto Hashizume

Int. J. Mol. Sci. 2015, 16(1), 148-158; doi:10.3390/ijms16010148

Received: 24 October 2014 / Accepted: 15 December 2014 / Published: 24 December 2014

Cited by 7 | PDF Full-text (2374 KB) | HTML Full-text | XML Full-text

Abstract

Matrix metalloproteinase 2 (MMP-2) in metastatic cancer tissue, which is associated with a poor prognosis, is a potential target for tumor imaging in vivo. Here, we describe a metastatic cancer cell-targeted protein nanocage. An MMP-2-binding peptide, termed CTT peptide (CTTHWGFTLC), was conjugated

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Matrix metalloproteinase 2 (MMP-2) in metastatic cancer tissue, which is associated with a poor prognosis, is a potential target for tumor imaging in vivo. Here, we describe a metastatic cancer cell-targeted protein nanocage. An MMP-2-binding peptide, termed CTT peptide (CTTHWGFTLC), was conjugated to the surface of a naturally occurring heat shock protein nanocage by genetic modification. The engineered protein nanocages showed a binding affinity for MMP-2 and selective uptake in cancer cells that highly expressed MMP-2 in vitro. In near-infrared fluorescence imaging, the nanocages showed specific and significant accumulation in tumor tissue after intravenous injection in vivo. These protein nanocages conjugated with CTT peptide could be potentially applied to a noninvasive near-infrared fluorescence detection method for imaging gelatinase activity in metastatic tumors in vivo. Full article

Open AccessReview The Potential of Liposomes with Carbonic Anhydrase IX to Deliver Anticancer Ingredients to Cancer Cells in Vivo

by Huei Leng Helena Ng, Aiping Lu, Ge Lin, Ling Qin and Zhijun Yang

Int. J. Mol. Sci. 2015, 16(1), 230-255; doi:10.3390/ijms16010230

Received: 4 November 2014 / Accepted: 16 December 2014 / Published: 24 December 2014

Cited by 5 | PDF Full-text (1060 KB) | HTML Full-text | XML Full-text

Abstract

Drug delivery nanocarriers, especially targeted drug delivery by liposomes are emerging as a class of therapeutics for cancer. Early research results suggest that liposomal therapeutics enhanced efficacy, while simultaneously reducing side effects, owing to properties such as more targeted localization in tumors and

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Drug delivery nanocarriers, especially targeted drug delivery by liposomes are emerging as a class of therapeutics for cancer. Early research results suggest that liposomal therapeutics enhanced efficacy, while simultaneously reducing side effects, owing to properties such as more targeted localization in tumors and active cellular uptake. Here, we highlight the features of immunoliposomes that distinguish them from previous anticancer therapies, and describe how these features provide the potential for therapeutic effects that are not achievable with other modalities. While a large number of studies has been published, the emphasis here is placed on the carbonic anhydrase IX (CA-IX) and the conjugated liposomes that are likely to open a new chapter on drug delivery system by using immunoliposomes to deliver anticancer ingredients to cancer cells in vivo. Full article

Open AccessArticle PLGA Biodegradable Nanoparticles Containing Perphenazine or Chlorpromazine Hydrochloride: Effect of Formulation and Release

by Mohammed Halayqa and Urszula Domańska

Int. J. Mol. Sci. 2014, 15(12), 23909-23923; doi:10.3390/ijms151223909

Received: 3 November 2014 / Revised: 8 December 2014 / Accepted: 12 December 2014 / Published: 22 December 2014

Cited by 11 | PDF Full-text (4227 KB) | HTML Full-text | XML Full-text

Abstract

In our study, poly(dl-lactide-co-glycolide) (PLGA) nanoparticles loaded with perphenazine (PPH) and chlorpromazine hydrochloride (CPZ-HCl) were formulated by emulsion solvent evaporation technique. The effect of various processing variables, including PLGA concentration, theoretical drug loading, poly(vinyl alcohol) (PVA) concentration and the power of sonication were

[...] Read more.

In our study, poly(dl-lactide-co-glycolide) (PLGA) nanoparticles loaded with perphenazine (PPH) and chlorpromazine hydrochloride (CPZ-HCl) were formulated by emulsion solvent evaporation technique. The effect of various processing variables, including PLGA concentration, theoretical drug loading, poly(vinyl alcohol) (PVA) concentration and the power of sonication were assessed systematically to obtain higher encapsulation efficiency and to minimize the nanoparticles size. By the optimization formulation process, the nanoparticles were obtained in submicron size from 325.5 ± 32.4 to 374.3 ± 10.1 nm for nanoparticles loaded with PPH and CPZ-HCl, respectively. Nanoparticles observed by scanning electron microscopy (SEM) presented smooth surface and spherical shape. The encapsulation efficiency of nanoparticles loaded with PPH and CPZ-HCl were 83.9% and 71.0%, respectively. The drug loading were 51.1% and 39.4% for PPH and CPZ-HCl, respectively. Lyophilized nanoparticles with different PLGA concentration 0.8%, 1.3% and 1.6% (w/v) in formulation process were evaluated for in vitro release in phosphate buffered saline (pH = 7.4) by using dialysis bags. The release profile for both drugs have shown that the rate of PPH and CPZ-HCl release were dependent on a size and amount of drugs in the nanoparticles. Full article

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Open AccessArticle Modulation of Induced Cytotoxicity of Doxorubicin by Using Apoferritin and Liposomal Cages

by Jaromir Gumulec, Michaela Fojtu, Martina Raudenska, Marketa Sztalmachova, Anna Skotakova, Jana Vlachova, Sylvie Skalickova, Lukas Nejdl, Pavel Kopel, Lucia Knopfova, Vojtech Adam, Rene Kizek, Marie Stiborova, Petr Babula and Michal Masarik

Int. J. Mol. Sci. 2014, 15(12), 22960-22977; doi:10.3390/ijms151222960

Received: 3 September 2014 / Revised: 6 November 2014 / Accepted: 1 December 2014 / Published: 11 December 2014

Cited by 20 | PDF Full-text (3483 KB) | HTML Full-text | XML Full-text

Abstract

Doxorubicin is an effective chemotherapeutic drug, however, its toxicity is a significant limitation in therapy. Encapsulation of doxorubicin inside liposomes or ferritin cages decreases cardiotoxicity while maintaining anticancer potency. We synthesized novel apoferritin- and liposome-encapsulated forms of doxorubicin (“Apodox” and “lip-8-dox”) and compared

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Doxorubicin is an effective chemotherapeutic drug, however, its toxicity is a significant limitation in therapy. Encapsulation of doxorubicin inside liposomes or ferritin cages decreases cardiotoxicity while maintaining anticancer potency. We synthesized novel apoferritin- and liposome-encapsulated forms of doxorubicin (“Apodox” and “lip-8-dox”) and compared its toxicity with doxorubicin and Myocet on prostate cell lines. Three different prostatic cell lines PNT1A, 22Rv1, and LNCaP were chosen. The toxicity of the modified doxorubicin forms was compared to conventional doxorubicin using the MTT assay, real-time cell impedance-based cell growth method (RTCA), and flow cytometry. The efficiency of doxorubicin entrapment was 56% in apoferritin cages and 42% in the liposome carrier. The accuracy of the RTCA system was verified by flow-cytometric analysis of cell viability. The doxorubicin half maximal inhibition concentrations (IC₅₀) were determined as 170.5, 234.0, and 169.0 nM for PNT1A, 22Rv1, and LNCaP, respectively by RTCA. Lip8-dox is less toxic on the non-tumor cell line PNT1A compared to doxorubicin, while still maintaining the toxicity to tumorous cell lines similar to doxorubicin or epirubicin (IC₅₀ = 2076.7 nM for PNT1A vs. 935.3 and 729.0 nM for 22Rv1 and LNCaP). Apodox IC₅₀ was determined as follows: 603.1, 1344.2, and 931.2 nM for PNT1A, 22Rv1, and LNCaP. Full article

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Open AccessArticle Polymer Coated CaAl-Layered Double Hydroxide Nanomaterials for Potential Calcium Supplement

by Tae-Hyun Kim, Jeong-A Lee, Soo-Jin Choi and Jae-Min Oh

Int. J. Mol. Sci. 2014, 15(12), 22563-22579; doi:10.3390/ijms151222563

Received: 31 October 2014 / Revised: 18 November 2014 / Accepted: 27 November 2014 / Published: 5 December 2014

Cited by 5 | PDF Full-text (3201 KB) | HTML Full-text | XML Full-text

Abstract

We have successfully prepared layered double hydroxide (LDH) nanomaterials containing calcium and aluminum ions in the framework (CaAl-LDH). The surface of CaAl-LDH was coated with enteric polymer, Eudragit^®L 100 in order to protect nanomaterials from fast dissolution under gastric condition of

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We have successfully prepared layered double hydroxide (LDH) nanomaterials containing calcium and aluminum ions in the framework (CaAl-LDH). The surface of CaAl-LDH was coated with enteric polymer, Eudragit^®L 100 in order to protect nanomaterials from fast dissolution under gastric condition of pH 1.2. The X-ray diffraction patterns, Fourier transform infrared spectroscopy, scanning electron and transmission electron microscopy revealed that the pristine LDH was well prepared having hydrocalumite structure, and that the polymer effectively coated the surface of LDH without disturbing structure. From thermal analysis, it was determined that only a small amount (less than 1%) of polymer was coated on the LDH surface. Metal dissolution from LDH nanomaterials was significantly reduced upon Eudragit^®L 100 coating at pH 1.2, 6.8 and 7.4, which simulates gastric, enteric and plasma conditions, respectively, and the dissolution effect was the most suppressed at pH 1.2. The LDH nanomaterials did not exhibit any significant cytotoxicity up to 1000 μg/mL and intracellular calcium concentration significantly increased in LDH-treated human intestinal cells. Pharmacokinetic study demonstrated absorption efficiency of Eudragit^®L 100 coated LDH following oral administration to rats. Moreover, the LDH nanomaterials did not cause acute toxic effect in vivo. All the results suggest the great potential of CaAl-LDH nanomaterials as a calcium supplement. Full article

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Open AccessArticle Some Characteristics of Free Cell Population in the Airways of Rats after Intratracheal Instillation of Copper-Containing Nano-Scale Particles

by Larisa I. Privalova, Boris A. Katsnelson, Nadezhda V. Loginova, Vladimir B. Gurvich, Vladimir Y. Shur, Yakov B. Beikin, Marina P. Sutunkova, Ilzira A. Minigalieva, Ekaterina V. Shishkina, Svetlana V. Pichugova, Ludmila G. Tulakina and Svetlana V. Beljayeva

Int. J. Mol. Sci. 2014, 15(11), 21538-21553; doi:10.3390/ijms151121538

Received: 8 August 2014 / Accepted: 12 November 2014 / Published: 24 November 2014

Cited by 3 | PDF Full-text (1857 KB) | HTML Full-text | XML Full-text

Abstract

We used stable water suspensions of copper oxide particles with mean diameter 20 nm and of particles containing copper oxide and element copper with mean diameter 340 nm to assess the pulmonary phagocytosis response of rats to a single intratracheal instillation of these

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We used stable water suspensions of copper oxide particles with mean diameter 20 nm and of particles containing copper oxide and element copper with mean diameter 340 nm to assess the pulmonary phagocytosis response of rats to a single intratracheal instillation of these suspensions using optical, transmission electron, and semi-contact atomic force microscopy and biochemical indices measured in the bronchoalveolar lavage fluid. Although both nano and submicron ultrafine particles were adversely bioactive, the former were found to be more toxic for lungs as compared with the latter while evoking more pronounced defense recruitment of alveolar macrophages and especially of neutrophil leukocytes and more active phagocytosis. Based on our results and literature data, we consider both copper solubilization and direct contact with cellular organelles (mainly, mitochondria) of persistent particles internalized by phagocytes as probable mechanisms of their cytotoxicity. Full article

Open AccessArticle Nickel Nanoparticles Exposure and Reproductive Toxicity in Healthy Adult Rats

by Lu Kong, Meng Tang, Ting Zhang, Dayong Wang, Ke Hu, Weiqi Lu, Chao Wei, Geyu Liang and Yuepu Pu

Int. J. Mol. Sci. 2014, 15(11), 21253-21269; doi:10.3390/ijms151121253

Received: 4 September 2014 / Revised: 5 November 2014 / Accepted: 10 November 2014 / Published: 17 November 2014

Cited by 15 | PDF Full-text (1127 KB) | HTML Full-text | XML Full-text

Abstract

Nickel is associated with reproductive toxicity. However, the reproductive toxicity of nickel nanoparticles (Ni NPs) is unclear. Our goal was to determine the association between nickel nanoparticle exposure and reproductive toxicity. According to the one-generation reproductive toxicity standard, rats were exposed to nickel

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Nickel is associated with reproductive toxicity. However, the reproductive toxicity of nickel nanoparticles (Ni NPs) is unclear. Our goal was to determine the association between nickel nanoparticle exposure and reproductive toxicity. According to the one-generation reproductive toxicity standard, rats were exposed to nickel nanoparticles by gavage and we selected indicators including sex hormone levels, sperm motility, histopathology, and reproductive outcome etc. Experimental results showed nickel nanoparticles increased follicle stimulating hormone (FSH) and luteinizing hormone (LH), and lowered etradiol (E₂) serum levels at a dose of 15 and 45 mg/kg in female rats. Ovarian lymphocytosis, vascular dilatation and congestion, inflammatory cell infiltration, and increase in apoptotic cells were found in ovary tissues in exposure groups. For male rats, the weights decreased gradually, the ratio of epididymis weight over body weight increased, the motility of rat sperm changed, and the levels of FSH and testosterone (T) diminished. Pathological results showed the shedding of epithelial cells of raw seminiferous tubule, disordered arrangement of cells in the tube, and the appearance of cell apoptosis and death in the exposure group. At the same time, Ni NPs resulted in a change of the reproductive index and the offspring development of rats. Further research is needed to elucidate exposure to human populations and mechanism of actions. Full article

Open AccessArticle Spectroscopic Studies of R(+)-α-Lipoic Acid—Cyclodextrin Complexes

by Naoko Ikuta, Akira Tanaka, Ayako Otsubo, Noriko Ogawa, Hiromitsu Yamamoto, Tomoyuki Mizukami, Shoji Arai, Masayuki Okuno, Keiji Terao and Seiichi Matsugo

Int. J. Mol. Sci. 2014, 15(11), 20469-20485; doi:10.3390/ijms151120469

Received: 8 September 2014 / Revised: 24 October 2014 / Accepted: 29 October 2014 / Published: 7 November 2014

Cited by 7 | PDF Full-text (3606 KB) | HTML Full-text | XML Full-text

Abstract

α-Lipoic acid (ALA) has a chiral center at the C6 position, and exists as two enantiomers, R(+)-ALA (RALA) and S(−)-ALA (SALA). RALA is naturally occurring, and is a cofactor for mitochondrial enzymes, therefore playing a major role in energy metabolism. However,

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α-Lipoic acid (ALA) has a chiral center at the C6 position, and exists as two enantiomers, R(+)-ALA (RALA) and S(−)-ALA (SALA). RALA is naturally occurring, and is a cofactor for mitochondrial enzymes, therefore playing a major role in energy metabolism. However, RALA cannot be used for pharmaceuticals or nutraceuticals because it readily polymerizes via a 1,2-dithiolane ring-opening when exposed to light or heat. So, it is highly desired to find out the method to stabilize RALA. The purpose of this study is to provide the spectroscopic information of stabilized RALA and SALA through complexation with cyclodextrins (CDs), α-CD, β-CD and γ-CD and to examine the physical characteristics of the resultant complexes in the solid state. The RALA-CD structures were elucidated based on the micro fourier transform infrared (FT-IR) and Raman analyses. The FT-IR results showed that the C=O stretching vibration of RALA appeared at 1717 cm⁻¹ and then shifted on formation of the RALA-CD complexes. The Raman spectra showed that the S–S and C–S stretching vibrations for RALA at 511 cm⁻¹ (S–S), 631 cm⁻¹ (C–S) and 675 cm⁻¹ (C–S) drastically weakened and almost disappeared upon complexation with CDs. Several peaks indicative of O–H vibrations also shifted or changed in intensity. These results indicate that RALA and CDs form host-guest complexes by interacting with one another. Full article

Open AccessArticle Heparin Assisted Photochemical Synthesis of Gold Nanoparticles and Their Performance as SERS Substrates

by Maria del Pilar Rodríguez-Torres, Luis Armando Díaz-Torres and Sergio Romero-Servin

Int. J. Mol. Sci. 2014, 15(10), 19239-19252; doi:10.3390/ijms151019239

Received: 2 September 2014 / Revised: 30 September 2014 / Accepted: 13 October 2014 / Published: 23 October 2014

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Abstract

Reactive and pharmaceutical-grade heparins were used as biologically compatible reducing and stabilizing agents to photochemically synthesize colloidal gold nanoparticles. Aggregates and anisotropic shapes were obtained photochemically under UV black-light lamp irradiation (λ = 366 nm). Heparin-functionalized gold nanoparticles were characterized by Scanning Electron

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Reactive and pharmaceutical-grade heparins were used as biologically compatible reducing and stabilizing agents to photochemically synthesize colloidal gold nanoparticles. Aggregates and anisotropic shapes were obtained photochemically under UV black-light lamp irradiation (λ = 366 nm). Heparin-functionalized gold nanoparticles were characterized by Scanning Electron Microscopy and UV-Vis spectroscopy. The negatively charged colloids were used for the Surface Enhanced Raman Spectroscopy (SERS) analysis of differently charged analytes (dyes). Measurements of pH were taken to inspect how the acidity of the medium affects the colloid-analyte interaction. SERS spectra were taken by mixing the dyes and the colloidal solutions without further functionalization or addition of any aggregating agent. Full article

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Open AccessArticle Discovery and in Vivo Evaluation of Novel RGD-Modified Lipid-Polymer Hybrid Nanoparticles for Targeted Drug Delivery

by Yinbo Zhao, Dayong Lin, Fengbo Wu, Li Guo, Gu He, Liang Ouyang, Xiangrong Song, Wei Huang and Xiang Li

Int. J. Mol. Sci. 2014, 15(10), 17565-17576; doi:10.3390/ijms151017565

Received: 25 July 2014 / Revised: 22 September 2014 / Accepted: 25 September 2014 / Published: 29 September 2014

Cited by 15 | PDF Full-text (3637 KB) | HTML Full-text | XML Full-text

Abstract

In the current study, the lipid-shell and polymer-core hybrid nanoparticles (lpNPs) modified by Arg–Gly–Asp(RGD) peptide, loaded with curcumin (Cur), were developed by emulsification-solvent volatilization method. The RGD-modified hybrid nanoparticles (RGD–lpNPs) could overcome the poor water solubility of Cur to meet the requirement of

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In the current study, the lipid-shell and polymer-core hybrid nanoparticles (lpNPs) modified by Arg–Gly–Asp(RGD) peptide, loaded with curcumin (Cur), were developed by emulsification-solvent volatilization method. The RGD-modified hybrid nanoparticles (RGD–lpNPs) could overcome the poor water solubility of Cur to meet the requirement of intravenous administration and tumor active targeting. The obtained optimal RGD-lpNPs, composed of PLGA (poly(lactic-co-glycolic acid))–mPEG (methoxyl poly(ethylene- glycol)), RGD–polyethylene glycol (PEG)–cholesterol (Chol) copolymers and lipids, had good entrapment efficiency, submicron size and negatively neutral surface charge. The core-shell structure of RGD–lpNPs was verified by TEM. Cytotoxicity analysis demonstrated that the RGD–lpNPs encapsulated Cur retained potent anti-tumor effects. Flow cytometry analysis revealed the cellular uptake of Cur encapsulated in the RGD–lpNPs was increased for human umbilical vein endothelial cells (HUVEC). Furthermore, Cur loaded RGD–lpNPs were more effective in inhibiting tumor growth in a subcutaneous B16 melanoma tumor model. The results of immunofluorescent and immunohistochemical studies by Cur loaded RGD–lpNPs therapies indicated that more apoptotic cells, fewer microvessels, and fewer proliferation-positive cells were observed. In conclusion, RGD–lpNPs encapsulating Cur were developed with enhanced anti-tumor activity in melanoma, and Cur loaded RGD–lpNPs represent an excellent tumor targeted formulation of Cur which might be an attractive candidate for cancer therapy. Full article

Open AccessArticle Emodin-Loaded Magnesium Silicate Hollow Nanocarriers for Anti-Angiogenesis Treatment through Inhibiting VEGF

by Hua Ren, Chao Zhu, Zhaohui Li, Wei Yang and E Song

Int. J. Mol. Sci. 2014, 15(9), 16936-16948; doi:10.3390/ijms150916936

Received: 3 August 2014 / Revised: 1 September 2014 / Accepted: 11 September 2014 / Published: 23 September 2014

Cited by 6 | PDF Full-text (2607 KB) | HTML Full-text | XML Full-text

Abstract

The applications of anti-VEGF (vascular endothelial growth factor) treatment in ophthalmic fields to inhibit angiogenesis have been widely documented in recent years. However, the hydrophobic nature of many agents makes its delivery difficult in practice. Therefore, the aim of the present study was

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The applications of anti-VEGF (vascular endothelial growth factor) treatment in ophthalmic fields to inhibit angiogenesis have been widely documented in recent years. However, the hydrophobic nature of many agents makes its delivery difficult in practice. Therefore, the aim of the present study was to introduce a new kind of hydrophobic drug carrier by employing nanoparticles with a hollow structure inside. Followed by the synthesis and characterization of magnesium silicate hollow spheres, cytotoxicity was evaluated in retina capillary endothelial cells. The loading and releasing capacity were tested by employing emodin, and the effect on VEGF expression was performed at the gene and protein level. Finally, an investigation on angiogenesis was carried on fertilized chicken eggs. The results indicated that the magnesium silicate nanoparticles had low toxicity. Emodin–MgSiO₃ can inhibit the expression of both VEGF gene and protein effectively. Angiogenesis of eggs was also reduced significantly. Based on the above results, we concluded that magnesium silicate hollow spheres were good candidates as drug carriers with enough safety. Full article

Open AccessArticle Self-Assembled Polymeric Micelles Based on Hyaluronic Acid-g-Poly(d,l-lactide-co-glycolide) Copolymer for Tumor Targeting

by Gyung Mo Son, Hyun Yul Kim, Je Ho Ryu, Chong Woo Chu, Dae Hwan Kang, Su Bum Park and Young-IL Jeong

Int. J. Mol. Sci. 2014, 15(9), 16057-16068; doi:10.3390/ijms150916057

Received: 30 June 2014 / Revised: 5 September 2014 / Accepted: 5 September 2014 / Published: 11 September 2014

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Abstract

Graft copolymer composed hyaluronic acid (HA) and poly(d,l-lactide-co-glycolide) (PLGA) (HAgLG) was synthesized for antitumor targeting via CD44 receptor of tumor cells. The carboxylic end of PLGA was conjugated with hexamethylenediamine (HMDA) to have amine end group in the end of chain (PLGA-amine). PLGA-amine

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Graft copolymer composed hyaluronic acid (HA) and poly(d,l-lactide-co-glycolide) (PLGA) (HAgLG) was synthesized for antitumor targeting via CD44 receptor of tumor cells. The carboxylic end of PLGA was conjugated with hexamethylenediamine (HMDA) to have amine end group in the end of chain (PLGA-amine). PLGA-amine was coupled with carboxylic acid of HA. Self-assembled polymeric micelles of HAgLG have spherical morphologies and their sizes were around 50–200 nm. Doxorubicin (DOX)-incorporated polymeric micelles were prepared by dialysis procedure. DOX was released over 4 days and its release rate was accelerated by the tumoric enzyme hyaluronidase. To assess targetability of polymeric micelles, CD44-positive HepG2 cells were employed treated with fluorescein isothiocyanate (FITC)-labeled polymeric micelles. HepG2 cells strongly expressed green fluorescence at the cell membrane and cytosol. However, internalization of polymeric micelles were significantly decreased when free HA was pretreated to block the CD44 receptor. Furthermore, the CD44-specific anticancer activity of HAgLG polymeric micelles was confirmed using CD44-negative CT26 cells and CD44-positive HepG2 cells. These results indicated that polymeric micelles of HaLG polymeric micelles have targetability against CD44 receptor of tumor cells. We suggest HAgLG polymeric micelles as a promising candidate for specific drug targeting. Full article

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Open AccessArticle Adsorption of Bisphenol A to a Carbon Nanotube Reduced Its Endocrine Disrupting Effect in Mice Male Offspring

by Wenwei Wang, Cuijuan Jiang, Ledong Zhu, Nana Liang, Xuejiao Liu, Jianbo Jia, Chengke Zhang, Shumei Zhai and Bin Zhang

Int. J. Mol. Sci. 2014, 15(9), 15981-15993; doi:10.3390/ijms150915981

Received: 30 June 2014 / Revised: 1 September 2014 / Accepted: 2 September 2014 / Published: 10 September 2014

Cited by 3 | PDF Full-text (1913 KB) | HTML Full-text | XML Full-text

Abstract

Soluble carbon nanotubes (CNTs) have shown promise as materials for adsorption of environmental contaminants such as Bisphenol A (BPA), due to the high adsorption capacity and strong desorption hysteresis of BPA on CNTs. The adsorption of BPA to CNTs may change the properties

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Soluble carbon nanotubes (CNTs) have shown promise as materials for adsorption of environmental contaminants such as Bisphenol A (BPA), due to the high adsorption capacity and strong desorption hysteresis of BPA on CNTs. The adsorption of BPA to CNTs may change the properties of both BPA and CNTs, and induce different toxicity to human and living systems from that of BPA and CNTs alone. Herein, we report that oral exposure of BPA/MWCNT–COOH (carboxylated multi-walled carbon nantubes) adduct to mice during gestation and lactation period decreased the male offspring reproductive toxicity compared with those induced by BPA alone. The adduct decreased malondialdehyde (MDA) level in testis and follicle-stimulating hormone (FSH) in serum, but increased the level of serum testosterone in male offspring in comparison to BPA alone. Our investigations broadened the knowledge of nanotoxicity and provided important information on the safe application of CNTs. Full article

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Open AccessReview Mechanistic Understanding of Toxicity from Nanocatalysts

by Cuijuan Jiang, Jianbo Jia and Shumei Zhai

Int. J. Mol. Sci. 2014, 15(8), 13967-13992; doi:10.3390/ijms150813967

Received: 16 June 2014 / Revised: 4 July 2014 / Accepted: 11 July 2014 / Published: 12 August 2014

Cited by 5 | PDF Full-text (1763 KB) | HTML Full-text | XML Full-text

Abstract

Nanoparticle-based catalysts, or nanocatalysts, have been applied in various industrial sectors, including refineries, petrochemical plants, the pharmaceutical industry, the chemical industry, food processing, and environmental remediation. As a result, there is an increasing risk of human exposure to nanocatalysts. This review evaluates the

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Nanoparticle-based catalysts, or nanocatalysts, have been applied in various industrial sectors, including refineries, petrochemical plants, the pharmaceutical industry, the chemical industry, food processing, and environmental remediation. As a result, there is an increasing risk of human exposure to nanocatalysts. This review evaluates the toxicity of popular nanocatalysts applied in industrial processes in cell and animal models. The molecular mechanisms associated with such nanotoxicity are emphasized to reveal common toxicity-inducing pathways from various nanocatalysts and the uniqueness of each specific nanocatalyst. Full article

Open AccessReview Biosurfactant Mediated Biosynthesis of Selected Metallic Nanoparticles

by Grażyna A. Płaza, Joanna Chojniak and Ibrahim M. Banat

Int. J. Mol. Sci. 2014, 15(8), 13720-13737; doi:10.3390/ijms150813720

Received: 29 May 2014 / Revised: 27 June 2014 / Accepted: 7 July 2014 / Published: 8 August 2014

Cited by 14 | PDF Full-text (1358 KB) | HTML Full-text | XML Full-text

Abstract

Developing a reliable experimental protocol for the synthesis of nanomaterials is one of the challenging topics in current nanotechnology particularly in the context of the recent drive to promote green technologies in their synthesis. The increasing need to develop clean, nontoxic and environmentally

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Developing a reliable experimental protocol for the synthesis of nanomaterials is one of the challenging topics in current nanotechnology particularly in the context of the recent drive to promote green technologies in their synthesis. The increasing need to develop clean, nontoxic and environmentally safe production processes for nanoparticles to reduce environmental impact, minimize waste and increase energy efficiency has become essential in this field. Consequently, recent studies on the use of microorganisms in the synthesis of selected nanoparticles are gaining increased interest as they represent an exciting area of research with considerable development potential. Microorganisms are known to be capable of synthesizing inorganic molecules that are deposited either intra- or extracellularly. This review presents a brief overview of current research on the use of biosurfactants in the biosynthesis of selected metallic nanoparticles and their potential importance. Full article

Open AccessArticle In Vivo Immunotoxicity of SiO2@(Y0.5Gd0.45Eu0.05)2O3 as Dual-Modality Nanoprobes

by Xiumei Tian, Ermao Li, Fanwen Yang, Ye Peng, Jixiang Zhu, Fupo He and Xiaoming Chen

Int. J. Mol. Sci. 2014, 15(8), 13649-13662; doi:10.3390/ijms150813649

Received: 29 April 2014 / Revised: 22 May 2014 / Accepted: 4 July 2014 / Published: 7 August 2014

PDF Full-text (1684 KB) | HTML Full-text | XML Full-text | Supplementary Files

Abstract

We have successfully synthesized SiO₂@(Y_0.₅Gd_0.45Eu_0.05)₂O₃ nanocomposites as a potential dual-modality nanoprobe for molecular imaging in vitro. However, their immunotoxicity assessment in vivo remains unknown. In this article, the in vitro

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We have successfully synthesized SiO₂@(Y_0.₅Gd_0.45Eu_0.05)₂O₃ nanocomposites as a potential dual-modality nanoprobe for molecular imaging in vitro. However, their immunotoxicity assessment in vivo remains unknown. In this article, the in vitro biocompatibility of our dual-modality nanoprobes was assayed in terms of cell viability and apoptosis. In vivo immunotoxicity was investigated by monitoring the generation of reactive oxygen species (ROS), cluster of differentiation (CD) markers and cytokines in Balb/c mice. The data show that the in vitro biocompatibility was satisfactory. In addition, the immunotoxicity data revealed there are no significant changes in the expression levels of CD11b and CD71 between the nanoprobe group and the Gd in a diethylenetriaminepentaacetic acid (DTPA) chelator (Gd-DTPA) group 24 h after injection in Balb/c mice (p > 0.05). Importantly, there are significant differences in the expression levels of CD206 and CD25 as well as the secretion of IL-4 and the generation of ROS 24 h after injection (p < 0.05). Transmission electron microscopy (TEM) images showed that few nanoprobes were localized in the phagosomes of liver and lung. In conclusion, the toxic effects of our nanoprobes may mainly result from the aggregation of particles in phagosomes. This accumulation may damage the microstructure of the cells and generate oxidative stress reactions that further stimulate the immune response. Therefore, it is important to evaluate the in vivo immunotoxicity of these rare earth-based biomaterials at the molecular level before molecular imaging in vivo. Full article

Open AccessArticle Subchronic Toxicity of Copper Oxide Nanoparticles and Its Attenuation with the Help of a Combination of Bioprotectors

by Larisa I. Privalova, Boris A. Katsnelson, Nadezhda V. Loginova, Vladimir B. Gurvich, Vladimir Y. Shur, Irene E. Valamina, Oleg H. Makeyev, Marina P. Sutunkova, Ilzira A. Minigalieva, Ekaterina P. Kireyeva, Vadim O. Rusakov, Anastasia E. Tyurnina, Roman V. Kozin, Ekaterina Y. Meshtcheryakova, Artem V. Korotkov, Eugene A. Shuman, Anastasia E. Zvereva and Svetlana V. Kostykova

Int. J. Mol. Sci. 2014, 15(7), 12379-12406; doi:10.3390/ijms150712379

Received: 7 May 2014 / Revised: 12 June 2014 / Accepted: 19 June 2014 / Published: 14 July 2014

Cited by 10 | PDF Full-text (1955 KB) | HTML Full-text | XML Full-text

Abstract

In the copper metallurgy workplace air is polluted with condensation aerosols, which a significant fraction of is presented by copper oxide particles <100 nm. In the scientific literature, there is a lack of their in vivo toxicity characterization and virtually no attempts of

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In the copper metallurgy workplace air is polluted with condensation aerosols, which a significant fraction of is presented by copper oxide particles <100 nm. In the scientific literature, there is a lack of their in vivo toxicity characterization and virtually no attempts of enhancing organism’s resistance to their impact. A stable suspension of copper oxide particles with mean (±SD) diameter 20 ± 10 nm was prepared by laser ablation of pure copper in water. It was being injected intraperitoneally to rats at a dose of 10 mg/kg (0.5 mg per mL of deionized water) three times a week up to 19 injections. In parallel, another group of rats was so injected with the same suspension against the background of oral administration of a “bio-protective complex” (BPC) comprising pectin, a multivitamin-multimineral preparation, some amino acids and fish oil rich in ω-3 PUFA. After the termination of injections, many functional and biochemical indices for the organism’s status, as well as pathological changes of liver, spleen, kidneys, and brain microscopic structure were evaluated for signs of toxicity. In the same organs we have measured accumulation of copper while their cells were used for performing the Random Amplification of Polymorphic DNA (RAPD) test for DNA fragmentation. The same features were assessed in control rats infected intraperitoneally with water with or without administration of the BPC. The copper oxide nanoparticles proved adversely bio-active in all respects considered in this study, their active in vivo solubilization in biological fluids playing presumably an important role in both toxicokinetics and toxicodynamics. The BPC proposed and tested by us attenuated systemic and target organs toxicity, as well as genotoxicity of this substance. Judging by experimental data obtained in this investigation, occupational exposures to nano-scale copper oxide particles can present a significant health risk while the further search for its management with the help of innocuous bioprotectors seems to be justified. Full article

Open AccessArticle Effects of Silica and Titanium Oxide Particles on a Human Neural Stem Cell Line: Morphology, Mitochondrial Activity, and Gene Expression of Differentiation Markers

by Kouki Fujioka, Sanshiro Hanada, Yuriko Inoue, Keisuke Sato, Kenji Hirakuri, Kouichi Shiraishi, Fumihide Kanaya, Keiichi Ikeda, Ritsuko Usui, Kenji Yamamoto, Seung U. Kim and Yoshinobu Manome

Int. J. Mol. Sci. 2014, 15(7), 11742-11759; doi:10.3390/ijms150711742

Received: 13 March 2014 / Revised: 25 May 2014 / Accepted: 16 June 2014 / Published: 2 July 2014

Cited by 8 | PDF Full-text (2136 KB) | HTML Full-text | XML Full-text

Abstract

Several in vivo studies suggest that nanoparticles (smaller than 100 nm) have the ability to reach the brain tissue. Moreover, some nanoparticles can penetrate into the brains of murine fetuses through the placenta by intravenous administration to pregnant mice. However, it is not

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Several in vivo studies suggest that nanoparticles (smaller than 100 nm) have the ability to reach the brain tissue. Moreover, some nanoparticles can penetrate into the brains of murine fetuses through the placenta by intravenous administration to pregnant mice. However, it is not clear whether the penetrated nanoparticles affect neurogenesis or brain function. To evaluate its effects on neural stem cells, we assayed a human neural stem cell (hNSCs) line exposed in vitro to three types of silica particles (30 nm, 70 nm, and <44 µm) and two types of titanium oxide particles (80 nm and < 44 µm). Our results show that hNSCs aggregated and exhibited abnormal morphology when exposed to the particles at concentrations = 0.1 mg/mL for 7 days. Moreover, all the particles affected the gene expression of Nestin (stem cell marker) and neurofilament heavy polypeptide (NF-H, neuron marker) at 0.1 mg/mL. In contrast, only 30-nm silica particles at 1.0 mg/mL significantly reduced mitochondrial activity. Notably, 30-nm silica particles exhibited acute membrane permeability at concentrations =62.5 µg/mL in 24 h. Although these concentrations are higher than the expected concentrations of nanoparticles in the brain from in vivo experiments in a short period, these thresholds may indicate the potential toxicity of accumulated particles for long-term usage or continuous exposure. Full article

Open AccessReview Potential for Layered Double Hydroxides-Based, Innovative Drug Delivery Systems

by Kai Zhang, Zhi Ping Xu, Ji Lu, Zhi Yong Tang, Hui Jun Zhao, David A. Good and Ming Qian Wei

Int. J. Mol. Sci. 2014, 15(5), 7409-7428; doi:10.3390/ijms15057409

Received: 14 February 2014 / Revised: 8 April 2014 / Accepted: 10 April 2014 / Published: 29 April 2014

Cited by 25 | PDF Full-text (711 KB) | HTML Full-text | XML Full-text

Abstract

Layered Double Hydroxides (LDHs)-based drug delivery systems have, for many years, shown great promises for the delivery of chemical therapeutics and bioactive molecules to mammalian cells in vitro and in vivo. This system offers high efficiency and drug loading density, as well as

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Layered Double Hydroxides (LDHs)-based drug delivery systems have, for many years, shown great promises for the delivery of chemical therapeutics and bioactive molecules to mammalian cells in vitro and in vivo. This system offers high efficiency and drug loading density, as well as excellent protection of loaded molecules from undesired degradation. Toxicological studies have also found LDHs to be biocompatible compared with other widely used nanoparticles, such as iron oxide, silica, and single-walled carbon nanotubes. A plethora of bio-molecules have been reported to either attach to the surface of or intercalate into LDH materials through co-precipitation or anion-exchange reaction, including amino acid and peptides, ATPs, vitamins, and even polysaccharides. Recently, LDHs have been used for gene delivery of small molecular nucleic acids, such as antisense, oligonucleotides, PCR fragments, siRNA molecules or sheared genomic DNA. These nano-medicines have been applied to target cells or organs in gene therapeutic approaches. This review summarizes current progress of the development of LDHs nanoparticle drug carriers for nucleotides, anti-inflammatory, anti-cancer drugs and recent LDH application in medical research. Ground breaking studies will be highlighted and an outlook of the possible future progress proposed. It is hoped that the layered inorganic material will open up new frontier of research, leading to new nano-drugs in clinical applications. Full article

Open AccessArticle Efficient Delivery of Plasmid DNA Using Cholesterol-Based Cationic Lipids Containing Polyamines and Ether Linkages

by Bieong-Kil Kim, Young-Bae Seu, Yun-Ui Bae, Tae-Won Kwak, Hyungu Kang, Ik-Jae Moon, Guen-Bae Hwang, So-Young Park and Kyung-Oh Doh

Int. J. Mol. Sci. 2014, 15(5), 7293-7312; doi:10.3390/ijms15057293

Received: 27 January 2014 / Revised: 24 March 2014 / Accepted: 10 April 2014 / Published: 28 April 2014

Cited by 6 | PDF Full-text (1458 KB) | HTML Full-text | XML Full-text

Abstract

Cationic liposomes are broadly used as non-viral vectors to deliver genetic materials that can be used to treat various diseases including cancer. To circumvent problems associated with cationic liposome-mediated delivery systems such as low transfection efficiency and serum-induced inhibition, cholesterol-based cationic lipids have

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Cationic liposomes are broadly used as non-viral vectors to deliver genetic materials that can be used to treat various diseases including cancer. To circumvent problems associated with cationic liposome-mediated delivery systems such as low transfection efficiency and serum-induced inhibition, cholesterol-based cationic lipids have been synthesized that resist the effects of serum. The introduction of an ether-type linkage and extension of the aminopropyl head group on the cholesterol backbone increased the transfection efficiency and DNA binding affinity compared to a carbamoyl-type linkage and a mono aminopropyl head group, respectively. Under optimal conditions, each liposome formulation showed higher transfection efficiency in AGS and Huh-7 cells than commercially available cationic liposomes, particularly in the presence of serum. The following molecular structures were found to have a positive effect on transfection properties: (i) extended aminopropyl head groups for a strong binding affinity to plasmid DNA; (ii) an ether linkage that favors electrostatic binding to plasmid DNA; and (iii) a cholesterol backbone for serum resistance. Full article

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Open AccessArticle Preparation and Characterization of Gelatin Nanofibers Containing Silver Nanoparticles

by Lim Jeong and Won Ho Park

Int. J. Mol. Sci. 2014, 15(4), 6857-6879; doi:10.3390/ijms15046857

Received: 18 February 2014 / Revised: 3 March 2014 / Accepted: 25 March 2014 / Published: 22 April 2014

Cited by 18 | PDF Full-text (1212 KB) | HTML Full-text | XML Full-text | Supplementary Files

Abstract

Ag nanoparticles (NPs) were synthesized in formic acid aqueous solutions through chemical reduction. Formic acid was used for a reducing agent of Ag precursor and solvent of gelatin. Silver acetate, silver tetrafluoroborate, silver nitrate, and silver phosphate were used as Ag precursors. Ag

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Ag nanoparticles (NPs) were synthesized in formic acid aqueous solutions through chemical reduction. Formic acid was used for a reducing agent of Ag precursor and solvent of gelatin. Silver acetate, silver tetrafluoroborate, silver nitrate, and silver phosphate were used as Ag precursors. Ag⁺ ions were reduced into Ag NPs by formic acid. The formation of Ag NPs was characterized by a UV-Vis spectrophotometer. Ag NPs were quickly generated within a few minutes in silver nitrate (AgNO₃)/formic acid solution. As the water content of formic acid aqueous solution increased, more Ag NPs were generated, at a higher rate and with greater size. When gelatin was added to the AgNO₃/formic acid solution, the Ag NPs were stabilized, resulting in smaller particles. Moreover, gelatin limits further aggregation of Ag NPs, which were effectively dispersed in solution. The amount of Ag NPs formed increased with increasing concentration of AgNO₃ and aging time. Gelatin nanofibers containing Ag NPs were fabricated by electrospinning. The average diameters of gelatin nanofibers were 166.52 ± 32.72 nm, but these decreased with the addition of AgNO₃. The average diameters of the Ag NPs in gelatin nanofibers ranged between 13 and 25 nm, which was confirmed by transmission electron microscopy (TEM). Full article

Open AccessReview Nanotoxicity Overview: Nano-Threat to Susceptible Populations

by Yang Li, Yi Zhang and Bing Yan

Int. J. Mol. Sci. 2014, 15(3), 3671-3697; doi:10.3390/ijms15033671

Received: 10 January 2014 / Revised: 9 February 2014 / Accepted: 13 February 2014 / Published: 28 February 2014

Cited by 28 | PDF Full-text (986 KB) | HTML Full-text | XML Full-text

Abstract

Due to the increasing applications of nanomaterials and nanotechnology, potential danger of nanoparticle exposure has become a critical issue. However, recent nanotoxicity studies have mainly focused on the health risks to healthy adult population. The nanotoxicity effects on susceptible populations (such as pregnant,

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Due to the increasing applications of nanomaterials and nanotechnology, potential danger of nanoparticle exposure has become a critical issue. However, recent nanotoxicity studies have mainly focused on the health risks to healthy adult population. The nanotoxicity effects on susceptible populations (such as pregnant, neonate, diseased, and aged populations) have been overlooked. Due to the alterations in physiological structures and functions in susceptible populations, they often suffer more damage from the same exposure. Thus, it is urgent to understand the effects of nanoparticle exposure on these populations. In order to fill this gap, the potential effects of nanoparticles to pregnant females, neonate, diseased, and aged population, as well as the possible underlying mechanisms are reviewed in this article. Investigations show that responses from susceptible population to nanoparticle exposure are often more severe. Reduced protection mechanism, compromised immunity, and impaired self-repair ability in these susceptible populations may contribute to the aggravated toxicity effects. This review will help minimize adverse effects of nanoparticles to susceptible population in future nanotechnology applications. Full article

Open AccessArticle Development of Lipid-Shell and Polymer Core Nanoparticles with Water-Soluble Salidroside for Anti-Cancer Therapy

by Dai-Long Fang, Yan Chen, Bei Xu, Ke Ren, Zhi-Yao He, Li-Li He, Yi Lei, Chun-Mei Fan and Xiang-Rong Song

Int. J. Mol. Sci. 2014, 15(3), 3373-3388; doi:10.3390/ijms15033373

Received: 17 December 2013 / Revised: 23 January 2014 / Accepted: 6 February 2014 / Published: 25 February 2014

Cited by 17 | PDF Full-text (544 KB) | HTML Full-text | XML Full-text

Abstract

Salidroside (Sal) is a potent antitumor drug with high water-solubility. The clinic application of Sal in cancer therapy has been significantly restricted by poor oral absorption and low tumor cell uptake. To solve this problem, lipid-shell and polymer-core nanoparticles (Sal-LPNPs) loaded with Sal

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Salidroside (Sal) is a potent antitumor drug with high water-solubility. The clinic application of Sal in cancer therapy has been significantly restricted by poor oral absorption and low tumor cell uptake. To solve this problem, lipid-shell and polymer-core nanoparticles (Sal-LPNPs) loaded with Sal were developed by a double emulsification method. The processing parameters including the polymer types, organic phase, PVA types and amount were systemically investigated. The obtained optimal Sal-LPNPs, composed of PLGA-PEG-PLGA triblock copolymers and lipids, had high entrapment efficiency (65%), submicron size (150 nm) and negatively charged surface (−23 mV). DSC analysis demonstrated the successful encapsulation of Sal into LPNPs. The core-shell structure of Sal-LPNPs was verified by TEM. Sal released slowly from the LPNPs without apparent burst release. MTT assay revealed that 4T1 and PANC-1 cancer cell lines were sensitive to Sal treatment. Sal-LPNPs had significantly higher antitumor activities than free Sal in 4T1 and PANC-1 cells. The data indicate that LPNPs are a promising Sal vehicle for anti-cancer therapy and worthy of further investigation. Full article

Open AccessArticle Dual Agent Loaded PLGA Nanoparticles Enhanced Antitumor Activity in a Multidrug-Resistant Breast Tumor Xenograft Model

by Yan Chen, Xue-Lian Zheng, Dai-Long Fang, Yang Yang, Jin-Kun Zhang, Hui-Li Li, Bei Xu, Yi Lei, Ke Ren and Xiang-Rong Song

Int. J. Mol. Sci. 2014, 15(2), 2761-2772; doi:10.3390/ijms15022761

Received: 30 December 2013 / Revised: 10 February 2014 / Accepted: 11 February 2014 / Published: 18 February 2014

Cited by 12 | PDF Full-text (344 KB) | HTML Full-text | XML Full-text

Abstract

Multidrug-resistant breast cancers have limited and ineffective clinical treatment options. This study aimed to develop PLGA nanoparticles containing a synergistic combination of vincristine and verapamil to achieve less toxicity and enhanced efficacy on multidrug-resistant breast cancers. The 1:250 molar ratio of VCR/VRP showed

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Multidrug-resistant breast cancers have limited and ineffective clinical treatment options. This study aimed to develop PLGA nanoparticles containing a synergistic combination of vincristine and verapamil to achieve less toxicity and enhanced efficacy on multidrug-resistant breast cancers. The 1:250 molar ratio of VCR/VRP showed strong synergism with the reversal index of approximately 130 in the multidrug-resistant MCF-7/ADR cells compared to drug-sensitive MCF-7 cells. The lyophilized nanoparticles could get dispersed quickly with the similar size distribution, zeta potential and encapsulation efficiency to the pre-lyophilized nanoparticles suspension, and maintain the synergistic in vitro release ratio of drugs. The co-encapsulated nanoparticle formulation had lower toxicity than free vincristine/verapamil combinations according to the acute-toxicity test. Furthermore, the most effective tumor growth inhibition in the MCF-7/ADR human breast tumor xenograft was observed in the co-delivery nanoparticle formulation group in comparison with saline control, free vincristine, free vincristine/verapamil combinations and single-drug nanoparticle combinations. All the data demonstrated that PLGANPs simultaneously loaded with chemotherapeutic drug and chemosensitizer might be one of the most potential formulations in the treatment of multidrug-resistant breast cancer in clinic. Full article

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Open AccessArticle Preparation and Characterization of Tripterygium wilfordii Multi-Glycoside Nanoparticle Using Supercritical Anti-Solvent Process

by Fengli Chen, Tong Li, Shuangyang Li, Kexin Hou, Zaizhi Liu, Lili Li, Guoqiang Cui, Yuangang Zu and Lei Yang

Int. J. Mol. Sci. 2014, 15(2), 2695-2711; doi:10.3390/ijms15022695

Received: 6 January 2014 / Revised: 25 January 2014 / Accepted: 10 February 2014 / Published: 17 February 2014

Cited by 4 | PDF Full-text (566 KB) | HTML Full-text | XML Full-text

Abstract

The aim of this study was to prepare nanosized Tripterygium wilfordii multi-glycoside (GTW) powders by the supercritical antisolvent precipitation process (SAS), and to evaluate the anti-inflammatory effects. Ethanol was used as solvent and carbon dioxide was used as an antisolvent. The effects of

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The aim of this study was to prepare nanosized Tripterygium wilfordii multi-glycoside (GTW) powders by the supercritical antisolvent precipitation process (SAS), and to evaluate the anti-inflammatory effects. Ethanol was used as solvent and carbon dioxide was used as an antisolvent. The effects of process parameters such as precipitation pressure (15–35 MPa), precipitation temperature (45–65 °C), drug solution flow rates (3–7 mL/min) and drug concentrations (10–30 mg/mL) were investigated. The nanospheres obtained with mean diameters ranged from 77.5 to 131.8 nm. The processed and unprocessed GTW were characterized by scanning electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy and thermal gravimetric analysis. The present study was designed to investigate the beneficial effect of the GTW nanoparticles on adjuvant-induced arthritis in albino rats. The processed and unprocessed GTW were tested against Freund’s complete adjuvant-induced arthritis in rats. Blood samples were collected for the estimation of interleukins (IL-1α, IL-1β) and tumor necrosis factor-α (TNF-α). It was concluded that physicochemical properties and anti-inflammatory activity of GTW nanoparticles could be improved by physical modification, such as particle size reduction using supercritical antisolvent (SAS) process. Further, SAS process was a powerful methodology for improving the physicochemical properties and anti-inflammatory activity of GTW. Full article

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Open AccessArticle The Preparation of Capsaicin-Chitosan Microspheres (CCMS) Enteric Coated Tablets

by Jian Chen, Gui-Dong Huang, Si-Rong Tan, Jiao Guo and Zheng-Quan Su

Int. J. Mol. Sci. 2013, 14(12), 24305-24319; doi:10.3390/ijms141224305

Received: 11 October 2013 / Revised: 10 December 2013 / Accepted: 12 December 2013 / Published: 13 December 2013

Cited by 9 | PDF Full-text (469 KB) | HTML Full-text | XML Full-text

Abstract

This study aimed to research the preparation and content determination of capsaicin-chitosan microspheres (CCMS) enteric coated tablets. The core tablets were prepared with the method of wet granulation. Nine formulae were designed to determine the optimal formula of the core tablet. Eudragit L100

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This study aimed to research the preparation and content determination of capsaicin-chitosan microspheres (CCMS) enteric coated tablets. The core tablets were prepared with the method of wet granulation. Nine formulae were designed to determine the optimal formula of the core tablet. Eudragit L100 was used to prepare the CCMS enteric-coated tablets. The effect of enteric coated formulation variables such as content of talc (10%, 25% and 40%), plasticisers (TEC and DBS), dosage of plasticiser (10%, 20% and 30%) and coating weight (2%, 3% and 5%) were evaluated for drug release characteristics. The in vitro release was studied using 0.1 N HCl and pH 6.8 phosphate buffer. Enteric coated tablets without ruptures or swelling behaviour over 2 h in 0.1 N HCl indicated that these tablets showed acid resistance. The accumulated release rate in phosphate buffer (pH 6.8) revealed that the prepared tablets were able to sustain drug release into the intestine and a first-order release was obtained for capsaicin. This research is the first report of the preparation and content determination of CCMS enteric coated tablets. The sustained release behavior of enteric coated formulations in pH 6.8 phosphate buffer demonstrated that it would be a potential drug delivery platform for sustained delivery of gastric irritant drugs. Full article

Open AccessArticle Comparability of in Vitro Tests for Bioactive Nanoparticles: A Common Assay to Detect Reactive Oxygen Species as an Example

by Matthias Roesslein, Cordula Hirsch, Jean-Pierre Kaiser, Harald F. Krug and Peter Wick

Int. J. Mol. Sci. 2013, 14(12), 24320-24337; doi:10.3390/ijms141224320

Received: 23 October 2013 / Revised: 10 December 2013 / Accepted: 11 December 2013 / Published: 13 December 2013

Cited by 14 | PDF Full-text (829 KB) | HTML Full-text | XML Full-text

Abstract

The release of reactive oxygen species (ROS) during the electron transport of mitochondrial aerobic respiration is the major source of ROS. However, contact between cells and nanoparticles (NPs) can also induce release of ROS, leading to an imbalance towards the pro-oxidative state. At

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The release of reactive oxygen species (ROS) during the electron transport of mitochondrial aerobic respiration is the major source of ROS. However, contact between cells and nanoparticles (NPs) can also induce release of ROS, leading to an imbalance towards the pro-oxidative state. At low levels of ROS production, cells initiate a protective response to guarantee their survival, but an excess of ROS can damage cellular compounds such as membranes and various organelles, or directly cause genotoxicity. Thus an elevated level of ROS is an important indicator of cellular stress and an accurate recording of this parameter would be very informative. ROS can be measured by various assays, but all known assays measuring and quantifying ROS possess certain weaknesses. The problems and challenges of quantitatively detecting ROS in vitro using the 2',7'-dichlorodihydrofluorescein (DCF) assay is discussed as an example. In addition, we debate the difficulties in finding a suitable and stable chemical reaction control for the DCF assay (or other ROS-detecting assays). As a conclusion, we believe that using 3-morpholinosydnonimine hydrochloride (Sin-1) as a ROS inducer in the DCF assay is feasible only qualitatively. However, a quantitative measurement of the absolute amount of ROS produced and a quantitative comparison between experiments is (at the moment) impossible. Full article

Open AccessArticle Optimized Production of Biodiesel from Waste Cooking Oil by Lipase Immobilized on Magnetic Nanoparticles

by Chi-Yang Yu, Liang-Yu Huang, I-Ching Kuan and Shiow-Ling Lee

Int. J. Mol. Sci. 2013, 14(12), 24074-24086; doi:10.3390/ijms141224074

Received: 9 October 2013 / Revised: 2 December 2013 / Accepted: 3 December 2013 / Published: 11 December 2013

Cited by 11 | PDF Full-text (328 KB) | HTML Full-text | XML Full-text

Abstract

Biodiesel, a non-toxic and biodegradable fuel, has recently become a major source of renewable alternative fuels. Utilization of lipase as a biocatalyst to produce biodiesel has advantages over common alkaline catalysts such as mild reaction conditions, easy product separation, and use of waste

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Biodiesel, a non-toxic and biodegradable fuel, has recently become a major source of renewable alternative fuels. Utilization of lipase as a biocatalyst to produce biodiesel has advantages over common alkaline catalysts such as mild reaction conditions, easy product separation, and use of waste cooking oil as raw material. In this study, Pseudomonas cepacia lipase immobilized onto magnetic nanoparticles (MNP) was used for biodiesel production from waste cooking oil. The optimal dosage of lipase-bound MNP was 40% (w/w of oil) and there was little difference between stepwise addition of methanol at 12 h- and 24 h-intervals. Reaction temperature, substrate molar ratio (methanol/oil), and water content (w/w of oil) were optimized using response surface methodology (RSM). The optimal reaction conditions were 44.2 °C, substrate molar ratio of 5.2, and water content of 12.5%. The predicted and experimental molar conversions of fatty acid methyl esters (FAME) were 80% and 79%, respectively. Full article

Open AccessArticle Self/Co-Assembling Peptide, EAR8-II, as a Potential Carrier for a Hydrophobic Anticancer Drug Pirarubicin (THP)—Characterization and in-Vitro Delivery

by Parisa Sadatmousavi and P. Chen

Int. J. Mol. Sci. 2013, 14(12), 23315-23329; doi:10.3390/ijms141223315

Received: 17 October 2013 / Revised: 13 November 2013 / Accepted: 14 November 2013 / Published: 26 November 2013

Cited by 6 | PDF Full-text (839 KB) | HTML Full-text | XML Full-text

Abstract

A short ionic-complementary peptide, EAR8-II, was employed to encapsulate the hydrophobic anticancer drug pirarubicin (THP). EAR8-II was designed to inherit advantages from two previously introduced peptides, AAP8 and EAK16-II, in their self/co-assembly. This peptide is short, simple, and inexpensive to synthesize, while possessing

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A short ionic-complementary peptide, EAR8-II, was employed to encapsulate the hydrophobic anticancer drug pirarubicin (THP). EAR8-II was designed to inherit advantages from two previously introduced peptides, AAP8 and EAK16-II, in their self/co-assembly. This peptide is short, simple, and inexpensive to synthesize, while possessing a low critical assembly concentration (CAC). The choice of alanine (A) residues in the peptide sequence provides moderate hydrophobic interactions, causing a minimal degree of aggregation, compared with other more hydrophobic residues. EAR8-II is an ionic-complementary peptide, similar to EAK16-II, can self/co-assemble with hydrophobic compounds such as THP, and forms a stable fibular nanostructure in aqueous solution. Physiochemical properties and cellular activities of the EAR8-II and THP complexes were evaluated and show dependency on the peptide-to-drug ratio. The complex at the peptide-to-drug mass ratio of 5:1 provides a stable solution, uniform nanostructure, and highly effective anticancer activity against various cancer cell lines. This work forms the basis for detailed studies on EAR8-II and THP formulations in vitro and in vivo, for future development of peptide-based delivery systems for hydrophobic anticancer drugs. Full article

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Open AccessArticle Size-Dependent Cytotoxicity of Nanocarbon Blacks

by Huating Kong, Yu Zhang, Yongjun Li, Zhifen Cui, Kai Xia, Yanhong Sun, Qunfen Zhao and Ying Zhu

Int. J. Mol. Sci. 2013, 14(11), 22529-22543; doi:10.3390/ijms141122529

Received: 22 September 2013 / Revised: 25 October 2013 / Accepted: 28 October 2013 / Published: 14 November 2013

Cited by 2 | PDF Full-text (1584 KB) | HTML Full-text | XML Full-text | Supplementary Files

Abstract

In this study, we investigated the toxic effects of nanocarbon blacks (NCBs) with different sizes to mouse macrophage RAW264.7 cells. MTT and fluorescence-based LIVE assays demonstrated that NCBs uptake caused a size and dose-dependent growth inhibition to the cells. Optical microscopy observations and

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In this study, we investigated the toxic effects of nanocarbon blacks (NCBs) with different sizes to mouse macrophage RAW264.7 cells. MTT and fluorescence-based LIVE assays demonstrated that NCBs uptake caused a size and dose-dependent growth inhibition to the cells. Optical microscopy observations and ^99mTc radionuclide labeling techniques were used to investigate the cellular uptake of NCBs with different sizes qualitatively and quantitatively, respectively. Results showed that the cellular uptake amounts of NCBs increased with their increasing size. Large quantities of internal NCBs induced oxidative stress and nuclear damage in cells; these effects may be the critical factors involved in the cytotoxicity of NCBs. The implications associated with these findings are discussed. Full article

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Open AccessArticle The Anti-Fasciolasis Properties of Silver Nanoparticles Produced by Trichoderma harzianum and Their Improvement of the Anti-Fasciolasis Drug Triclabendazole

by Youssuf A. Gherbawy, Ismail M. Shalaby, Mahmoud Syed Abd El-sadek, Hesham M. Elhariry and AbdelElah A. Banaja

Int. J. Mol. Sci. 2013, 14(11), 21887-21898; doi:10.3390/ijms141121887

Received: 22 September 2013 / Revised: 21 October 2013 / Accepted: 28 October 2013 / Published: 5 November 2013

Cited by 4 | PDF Full-text (379 KB) | HTML Full-text | XML Full-text

Abstract

Recently, new strains of Fasciola demonstrated drug resistance, which increased the need for new drugs or improvement of the present drugs. Nanotechnology is expected to open some new opportunities to fight and prevent diseases using an atomic scale tailoring of materials. The ability

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Recently, new strains of Fasciola demonstrated drug resistance, which increased the need for new drugs or improvement of the present drugs. Nanotechnology is expected to open some new opportunities to fight and prevent diseases using an atomic scale tailoring of materials. The ability to uncover the structure and function of biosystems at the nanoscale, stimulates research leading to improvement in biology, biotechnology, medicine and healthcare. The size of nanomaterials is similar to that of most biological molecules and structures; therefore, nanomaterials can be useful for both in vivo and in vitro biomedical research and applications. Therefore, this work aimed to isolate fungal strains from Taif soil samples, which have the ability to synthesize silver nanoparticles. The fungus Trichoderma harzianum, when challenged with silver nitrate solution, accumulated silver nanoparticles (AgNBs) on the surface of its cell wall in 72 h. These nanoparticles, dislodged by ultrasonication, showed an absorption peak at 420 nm in a UV-visible spectrum, corresponding to the plasmon resonance of silver nanoparticles. The transmission electron micrographs of dislodged nanoparticles in aqueous solution showed the production of reasonably monodisperse silver nanoparticles (average particle size: 4.66 nm) by the fungus. The percentage of non hatching eggs treated with the Triclabendazole drug was 69.67%, while this percentage increased to 89.67% in combination with drug and AgNPs. Full article

Open AccessArticle Fast Disintegrating Quercetin-Loaded Drug Delivery Systems Fabricated Using Coaxial Electrospinning

by Xiao-Yan Li, Yan-Chun Li, Deng-Guang Yu, Yao-Zu Liao and Xia Wang

Int. J. Mol. Sci. 2013, 14(11), 21647-21659; doi:10.3390/ijms141121647

Received: 12 October 2013 / Revised: 26 October 2013 / Accepted: 28 October 2013 / Published: 31 October 2013

Cited by 13 | PDF Full-text (1608 KB) | HTML Full-text | XML Full-text

Abstract

The objective of this study is to develop a structural nanocomposite of multiple components in the form of core-sheath nanofibres using coaxial electrospinning for the fast dissolving of a poorly water-soluble drug quercetin. Under the selected conditions, core-sheath nanofibres with quercetin and sodium

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The objective of this study is to develop a structural nanocomposite of multiple components in the form of core-sheath nanofibres using coaxial electrospinning for the fast dissolving of a poorly water-soluble drug quercetin. Under the selected conditions, core-sheath nanofibres with quercetin and sodium dodecyl sulphate (SDS) distributed in the core and sheath part of nanofibres, respectively, were successfully generated, and the drug content in the nanofibres was able to be controlled simply through manipulating the core fluid flow rates. Field emission scanning electron microscope (FESEM) images demonstrated that the nanofibres prepared from the single sheath fluid and double core/sheath fluids (with core-to-sheath flow rate ratios of 0.4 and 0.7) have linear morphology with a uniform structure and smooth surface. The TEM images clearly demonstrated the core-sheath structures of the produced nanocomposites. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) results verified that quercetin and SDS were well distributed in the polyvinylpyrrolidone (PVP) matrix in an amorphous state, due to the favourite second-order interactions. In vitro dissolution studies showed that the core-sheath composite nanofibre mats could disintegrate rapidly to release quercetin within 1 min. The study reported here provides an example of the systematic design, preparation, characterization and application of a new type of structural nanocomposite as a fast-disintegrating drug delivery system. Full article

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Open AccessArticle Preparation and Characterization of Nanoliposomes Entrapping Medium-Chain Fatty Acids and Vitamin C by Lyophilization

by Shuibing Yang, Chengmei Liu, Wei Liu, Haixia Yu, Huijuan Zheng, Wei Zhou and Yaqin Hu

Int. J. Mol. Sci. 2013, 14(10), 19763-19773; doi:10.3390/ijms141019763

Received: 15 July 2013 / Revised: 12 September 2013 / Accepted: 22 September 2013 / Published: 30 September 2013

Cited by 8 | PDF Full-text (136 KB) | HTML Full-text | XML Full-text

Abstract

The complex nanoliposomes encapsulating both a hydrophilic drug vitamin C (vit C) and hydrophobic drug medium-chain fatty acids (MCFAs) was prepared by combining double emulsion method with dynamic high pressure microfluidization. The complex nanoliposomes was further freeze-dried under −86 °C for 48 h

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The complex nanoliposomes encapsulating both a hydrophilic drug vitamin C (vit C) and hydrophobic drug medium-chain fatty acids (MCFAs) was prepared by combining double emulsion method with dynamic high pressure microfluidization. The complex nanoliposomes was further freeze-dried under −86 °C for 48 h with sucrose at the sucrose/lipids ratio of 2:1(w/w) in order to enhance its stability. The freeze-dried complex nanoliposomes under the suitable conditions exhibited high entrapment efficiency of MCFAs (44.26 ± 3.34)%, relatively high entrapment efficiency of vit C (62.25 ± 3.43)%, low average size diameter (110.4 ± 7.28) nm and good storage stability at 4 °C for 60 days with slight changes in mean particle diameter and drug entrapment efficiencies. The results of transmission electron microscopy of freeze-dried complex nanoliposomes also showed that the freeze-dried samples with sucrose were stable without great increase in their particle sizes and without destroying their spherical shape. The results indicated that sucrose presented well protection effects in MCFAs-vit C complex nanoliposomes, suggesting the possibility of further usage in commercial liposomes. Full article

Open AccessReview The Effects of Nanomaterials as Endocrine Disruptors

by Ivo Iavicoli, Luca Fontana, Veruscka Leso and Antonio Bergamaschi

Int. J. Mol. Sci. 2013, 14(8), 16732-16801; doi:10.3390/ijms140816732

Received: 30 May 2013 / Revised: 8 July 2013 / Accepted: 25 July 2013 / Published: 14 August 2013

Cited by 47 | PDF Full-text (1177 KB) | HTML Full-text | XML Full-text

Abstract

In recent years, nanoparticles have been increasingly used in several industrial, consumer and medical applications because of their unique physico-chemical properties. However, in vitro and in vivo studies have demonstrated that these properties are also closely associated with detrimental health effects. There is

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In recent years, nanoparticles have been increasingly used in several industrial, consumer and medical applications because of their unique physico-chemical properties. However, in vitro and in vivo studies have demonstrated that these properties are also closely associated with detrimental health effects. There is a serious lack of information on the potential nanoparticle hazard to human health, particularly on their possible toxic effects on the endocrine system. This topic is of primary importance since the disruption of endocrine functions is associated with severe adverse effects on human health. Consequently, in order to gather information on the hazardous effects of nanoparticles on endocrine organs, we reviewed the data available in the literature regarding the endocrine effects of in vitro and in vivo exposure to different types of nanoparticles. Our aim was to understand the potential endocrine disrupting risks posed by nanoparticles, to assess their underlying mechanisms of action and identify areas in which further investigation is needed in order to obtain a deeper understanding of the role of nanoparticles as endocrine disruptors. Current data support the notion that different types of nanoparticles are capable of altering the normal and physiological activity of the endocrine system. However, a critical evaluation of these findings suggests the need to interpret these results with caution since information on potential endocrine interactions and the toxicity of nanoparticles is quite limited. Full article

Open AccessArticle Galactosylated Chitosan Oligosaccharide Nanoparticles for Hepatocellular Carcinoma Cell-Targeted Delivery of Adenosine Triphosphate

by Xiu Liang Zhu, Yong Zhong Du, Ri Sheng Yu, Ping Liu, Dan Shi, Ying Chen, Ying Wang and Fang Fang Huang

Int. J. Mol. Sci. 2013, 14(8), 15755-15766; doi:10.3390/ijms140815755

Received: 27 April 2013 / Revised: 7 July 2013 / Accepted: 23 July 2013 / Published: 29 July 2013

Cited by 16 | PDF Full-text (575 KB) | HTML Full-text | XML Full-text

Abstract

Nanoparticles composed of galactosylated chitosan oligosaccharide (Gal-CSO) and adenosine triphosphate (ATP) were prepared for hepatocellular carcinoma cell-specific uptake, and the characteristics of Gal-CSO/ATP nanoparticles were evaluated. CSO/ATP nanoparticles were prepared as a control. The average diameter and zeta potential of Gal-CSO/ATP nanoparticles were

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Nanoparticles composed of galactosylated chitosan oligosaccharide (Gal-CSO) and adenosine triphosphate (ATP) were prepared for hepatocellular carcinoma cell-specific uptake, and the characteristics of Gal-CSO/ATP nanoparticles were evaluated. CSO/ATP nanoparticles were prepared as a control. The average diameter and zeta potential of Gal-CSO/ATP nanoparticles were 51.03 ± 3.26 nm and 30.50 ± 1.25 mV, respectively, suggesting suitable properties for a drug delivery system. Subsequently, the cytotoxicity of Gal-CSO/ATP nanoparticles were examined by the methyl tetrazolium (MTT) assay, and the half maximal inhibitory concentration (IC₅₀) values were calculated with HepG2 (human hepatocellular carcinoma cell line) cells. The results showed that the cytotoxic effect of nanoparticles on HepG2 cells was low. In the meantime, it was also found that the Gal-CSO/ATP nanoparticles could be uptaken by HepG2 cells, due to expression of the asialoglycoprotein receptor (ASGP-R) on their surfaces. The presented results indicate that the Gal-CSO nanoparticles might be very attractive to be used as an intracellular drug delivery carrier for hepatocellular carcinoma cell targeting, thus warranting further in vivo or clinical investigations. Full article

Open AccessArticle Synergistic Effects of Nano-Sized Titanium Dioxide and Zinc on the Photosynthetic Capacity and Survival of Anabaena sp.

by Yulin Tang, Shuyan Li, Junlian Qiao, Hongtao Wang and Lei Li

Int. J. Mol. Sci. 2013, 14(7), 14395-14407; doi:10.3390/ijms140714395

Received: 1 April 2013 / Revised: 24 June 2013 / Accepted: 24 June 2013 / Published: 11 July 2013

Cited by 9 | PDF Full-text (379 KB) | HTML Full-text | XML Full-text | Supplementary Files

Abstract

Anabaena sp. was used to examine the toxicity of exposure to a nano-TiO₂ suspension, Zn²⁺ solution, and mixtures of nano-TiO₂ and Zn²⁺ suspensions. Typical chlorophyll fluorescence parameters, including effective quantum yield, photosynthetic efficiency and maximal electron transport rate, were

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Anabaena sp. was used to examine the toxicity of exposure to a nano-TiO₂ suspension, Zn²⁺ solution, and mixtures of nano-TiO₂ and Zn²⁺ suspensions. Typical chlorophyll fluorescence parameters, including effective quantum yield, photosynthetic efficiency and maximal electron transport rate, were measured by a pulse-amplitude modulated fluorometer. Nano-TiO₂ particles exhibited no significant toxicity at concentrations lower than 10.0 mg/L. The 96 h concentration for the 50% maximal effect (EC₅₀) of Zn²⁺ alone to Anabaena sp. was 0.38 ± 0.004 mg/L. The presence of nano-TiO₂ at low concentrations (<1.0 mg/L) significantly enhanced the toxicity of Zn²⁺ and consequently reduced the EC₅₀ value to 0.29 ± 0.003 mg/L. However, the toxicity of the Zn²⁺/TiO₂ system decreased with increasing nano-TiO₂ concentration because of the substantial adsorption of Zn²⁺ by nano-TiO₂. The toxicity curve of the Zn²⁺/TiO₂ system as a function of incremental nano-TiO₂ concentrations was parabolic. The toxicity significantly increased at the initial stage, reached its maximum, and then decreased with increasing nano-TiO₂ concentration. Hydrodynamic sizes, concentration of nano-TiO₂ and Zn²⁺ loaded nano-TiO₂ were the main parameters for synergistic toxicity. Full article

Open AccessArticle Non-Covalent Synthesis of Metal Oxide Nanoparticle–Heparin Hybrid Systems: A New Approach to Bioactive Nanoparticles

by Elena Vismara, Antonio Valerio, Alessia Coletti, Giangiacomo Torri, Sabrina Bertini, Giorgio Eisele, Rosalba Gornati and Giovanni Bernardini

Int. J. Mol. Sci. 2013, 14(7), 13463-13481; doi:10.3390/ijms140713463

Received: 1 March 2013 / Revised: 24 May 2013 / Accepted: 14 June 2013 / Published: 27 June 2013

Cited by 5 | PDF Full-text (2873 KB) | HTML Full-text | XML Full-text

Abstract

Heparin has been conjugated to Fe₃O₄, Co₃O₄, and NiO nanoparticles (NPs) through electrostatic interactions, producing colloidal suspensions of hybrid metal oxide heparin NPs that are stable in water. Negative zeta potentials and retention of heparin’s

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Heparin has been conjugated to Fe₃O₄, Co₃O₄, and NiO nanoparticles (NPs) through electrostatic interactions, producing colloidal suspensions of hybrid metal oxide heparin NPs that are stable in water. Negative zeta potentials and retention of heparin’s ability to capture toluidine blue indicate that heparin’s negative charges are exposed on the surface of the coated NPs. IR results confirmed the formation of nanohybrids as did NMR experiments, which were also interpreted on the basis of toluidine blue tests. Transmission electron microscopy results revealed that the heparin coating does not modify the shape or dimension of the NPs. Dynamic light scattering and negative zeta potential measurements confirmed that heparin surface functionalisation is an effective strategy to prevent NP aggregation. Full article

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Open AccessArticle Voltammetry as a Tool for Characterization of CdTe Quantum Dots

by Pavlina Sobrova, Marketa Ryvolova, Jaromir Hubalek, Vojtech Adam and Rene Kizek

Int. J. Mol. Sci. 2013, 14(7), 13497-13510; doi:10.3390/ijms140713497

Received: 22 April 2013 / Revised: 6 May 2013 / Accepted: 20 May 2013 / Published: 27 June 2013

Cited by 9 | PDF Full-text (938 KB) | HTML Full-text | XML Full-text

Abstract

Electrochemical detection of quantum dots (QDs) has already been used in numerous applications. However, QDs have not been well characterized using voltammetry, with respect to their characterization and quantification. Therefore, the main aim was to characterize CdTe QDs using cyclic and differential pulse

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Electrochemical detection of quantum dots (QDs) has already been used in numerous applications. However, QDs have not been well characterized using voltammetry, with respect to their characterization and quantification. Therefore, the main aim was to characterize CdTe QDs using cyclic and differential pulse voltammetry. The obtained peaks were identified and the detection limit (3 S/N) was estimated down to 100 fg/mL. Based on the convincing results, a new method for how to study stability and quantify the dots was suggested. Thus, the approach was further utilized for the testing of QDs stability. Full article

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Open AccessArticle An Ultrasensitive Electrochemiluminescence Immunoassay for Carbohydrate Antigen 19-9 in Serum Based on Antibody Labeled Fe₃O₄ Nanoparticles as Capture Probes and Graphene/CdTe Quantum Dot Bionanoconjugates as Signal Amplifiers

by Ning Gan, Jing Zhou, Ping Xiong, Tianhua Li, Shan Jiang, Yuting Cao and Qianli Jiang

Int. J. Mol. Sci. 2013, 14(5), 10397-10411; doi:10.3390/ijms140510397

Received: 1 February 2013 / Revised: 2 May 2013 / Accepted: 6 May 2013 / Published: 17 May 2013

Cited by 7 | PDF Full-text (867 KB) | HTML Full-text | XML Full-text

Abstract

The CdTe quantum dots (QDs), graphene nanocomposite (CdTe-G) and dextran–Fe₃O₄ magnetic nanoparticles have been synthesized for developing an ultrasensitive electrochemiluminescence (ECL) immunoassay for Carcinoembryonic antigen 19-9 (CA 19-9) in serums. Firstly, the capture probes (CA 19-9 Ab1/Fe₃O₄

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The CdTe quantum dots (QDs), graphene nanocomposite (CdTe-G) and dextran–Fe₃O₄ magnetic nanoparticles have been synthesized for developing an ultrasensitive electrochemiluminescence (ECL) immunoassay for Carcinoembryonic antigen 19-9 (CA 19-9) in serums. Firstly, the capture probes (CA 19-9 Ab1/Fe₃O₄) for enriching CA 19-9 were synthesized by immobilizing the CA 19-9’s first antibody (CA 19-9 Ab1) on magnetic nanoparticles (dextran-Fe₃O₄). Secondly, the signal probes (CA 19-9 Ab2/CdTe-G), which can emit an ECL signal, were formed by attaching the secondary CA 19-9 antibody (CA 19-9 Ab2) to the surface of the CdTe-G. Thirdly, the above two probes were used for conjugating with a serial of CA 19-9 concentrations. Graphene can immobilize dozens of CdTe QDs on their surface, which can emit stronger ECL intensity than CdTe QDs. Based on the amplified signal, ultrasensitive antigen detection can be realized. Under the optimal conditions, the ECL signal depended linearly on the logarithm of CA 19-9 concentration from 0.005 to 100 pg/mL, and the detection limit was 0.002 pg/mL. Finally, five samples of human serum were tested, and the results were compared with a time-resolved fluorescence assay (TRFA). The novel immunoassay provides a stable, specific and highly sensitive immunoassay protocol for tumor marker detection at very low levels, which can be applied in early diagnosis of tumor. Full article

Open AccessReview Effects of Nanotoxicity on Female Reproductivity and Fetal Development in Animal Models

by Jianling Sun, Qiu Zhang, Zhiping Wang and Bing Yan

Int. J. Mol. Sci. 2013, 14(5), 9319-9337; doi:10.3390/ijms14059319

Received: 28 February 2013 / Revised: 17 April 2013 / Accepted: 18 April 2013 / Published: 29 April 2013

Cited by 25 | PDF Full-text (1217 KB) | HTML Full-text | XML Full-text

Abstract

The extensive application of nanomaterials in industry, medicine and consumer products has raised concerns about their potential toxicity. The female population is particularly vulnerable and deserves special attention because toxicity in this group may impact both female reproductivity and fetal development. Mouse and

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The extensive application of nanomaterials in industry, medicine and consumer products has raised concerns about their potential toxicity. The female population is particularly vulnerable and deserves special attention because toxicity in this group may impact both female reproductivity and fetal development. Mouse and zebrafish models each have their own unique features and studies using these models to examine the potential toxicity of various nanoparticles are compared and summarized in this review. Several nanoparticles exhibit detrimental effects on female reproductivity as well as fetal development, and these adverse effects are related to nanoparticle composition, surface modification, dose, exposure route and animal species. Limited studies on the mechanisms of nanotoxicity are also documented and reviewed herein. Full article

Open AccessArticle Growth and Potential Damage of Human Bone-Derived Cells on Fresh and Aged Fullerene C₆₀ Films

by Ivana Kopova, Lucie Bacakova, Vasily Lavrentiev and Jiri Vacik

Int. J. Mol. Sci. 2013, 14(5), 9182-9204; doi:10.3390/ijms14059182

Received: 15 January 2013 / Revised: 10 April 2013 / Accepted: 15 April 2013 / Published: 26 April 2013

Cited by 6 | PDF Full-text (6048 KB) | HTML Full-text | XML Full-text

Abstract

Fullerenes are nanoparticles composed of carbon atoms arranged in a spherical hollow cage-like structure. Numerous studies have evaluated the therapeutic potential of fullerene derivates against oxidative stress-associated conditions, including the prevention or treatment of arthritis. On the other hand, fullerenes are not only

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Fullerenes are nanoparticles composed of carbon atoms arranged in a spherical hollow cage-like structure. Numerous studies have evaluated the therapeutic potential of fullerene derivates against oxidative stress-associated conditions, including the prevention or treatment of arthritis. On the other hand, fullerenes are not only able to quench, but also to generate harmful reactive oxygen species. The reactivity of fullerenes may change in time due to the oxidation and polymerization of fullerenes in an air atmosphere. In this study, we therefore tested the dependence between the age of fullerene films (from one week to one year) and the proliferation, viability and metabolic activity of human osteosarcoma cells (lines MG-63 and U-2 OS). We also monitored potential membrane and DNA damage and morphological changes of the cells. After seven days of cultivation, we did not observe any cytotoxic morphological changes, such as enlarged cells or cytosolic vacuole formation. Furthermore, there was no increased level of DNA damage. The increasing age of the fullerene films did not cause enhancement of cytotoxicity. On the contrary, it resulted in an improvement in the properties of these materials, which are more suitable for cell cultivation. Therefore, fullerene films could be considered as a promising material with potential use as a bioactive coating of cell carriers for bone tissue engineering. Full article

Open AccessArticle Magnetic Drug Targeting Reduces the Chemotherapeutic Burden on Circulating Leukocytes

by Christina Janko, Stephan Dürr, Luis E. Munoz, Stefan Lyer, Ricardo Chaurio, Rainer Tietze, Sarah von Löhneysen, Christine Schorn, Martin Herrmann and Christoph Alexiou

Int. J. Mol. Sci. 2013, 14(4), 7341-7355; doi:10.3390/ijms14047341

Received: 3 December 2012 / Revised: 8 March 2013 / Accepted: 8 March 2013 / Published: 2 April 2013

Cited by 24 | PDF Full-text (1858 KB) | HTML Full-text | XML Full-text

Abstract

Magnetic drug targeting (MDT) improves the integrity of healthy tissues and cells during treatment with cytotoxic drugs. An anticancer drug is bound to superparamagnetic iron oxide nanoparticles (SPION), injected into the vascular supply of the tumor and directed into the tumor by means

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Magnetic drug targeting (MDT) improves the integrity of healthy tissues and cells during treatment with cytotoxic drugs. An anticancer drug is bound to superparamagnetic iron oxide nanoparticles (SPION), injected into the vascular supply of the tumor and directed into the tumor by means of an external magnetic field. In this study, we investigated the impact of SPION, mitoxantrone (MTO) and SPION^MTO on cell viability in vitro and the nonspecific uptake of MTO into circulating leukocytes in vivo. MDT was compared with conventional chemotherapy. MTO uptake and the impact on cell viability were assessed by flow cytometry in a Jurkat cell culture. In order to analyze MTO loading of circulating leukocytes in vivo, we treated tumor-bearing rabbits with MDT and conventional chemotherapy. In vitro experiments showed a dose-dependent MTO uptake and reduction in the viability and proliferation of Jurkat cells. MTO and SPION^MTO showed similar cytotoxic activity. Non-loaded SPION did not have any effect on cell viability in the concentrations tested. Compared with systemic administration in vivo, MDT employing SPION^MTO significantly decreased the chemotherapeutic load in circulating leukocytes. We demonstrated that MDT spares the immune system in comparison with conventional chemotherapy. Full article

Open AccessArticle Trends in Nanopharmaceutical Patents

by Adelaide Antunes, Iolanda Fierro, Rafaela Guerrante, Flavia Mendes and Maria Simone de M. Alencar

Int. J. Mol. Sci. 2013, 14(4), 7016-7031; doi:10.3390/ijms14047016

Received: 28 December 2012 / Revised: 14 March 2013 / Accepted: 15 March 2013 / Published: 27 March 2013

Cited by 5 | PDF Full-text (219 KB) | HTML Full-text | XML Full-text

Abstract

Investment in nanotechnology is now a given constant by governments, research centers and companies in both more developed countries and emerging markets. Due to their characteristics, such as high stability, ability to enable antigen identification on specific cells in the human body and

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Investment in nanotechnology is now a given constant by governments, research centers and companies in both more developed countries and emerging markets. Due to their characteristics, such as high stability, ability to enable antigen identification on specific cells in the human body and controlling the release of drugs and, therefore, improving therapies, nanoparticles have been the subject of research and patent applications in the pharmaceutical field. According to the Organization for Economic Co-operation and Development (OCDE), patent data can be used as a source of information in order to measure science and technology activities. Thereby, this paper presents an analysis based on patent documents related to nanotechnology in the pharmaceutical sector. As a result, the analysis of patents demonstrate primarily that nanobiotechnology attracts high levels of R&D investments, including nanoparticle-based chemotherapeutic agents/drugs, monoclonal antibody nanoparticle complexes and their role in drug delivery or contrast agents with non-toxic effects. Full article

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Open AccessArticle Active Silver Nanoparticles for Wound Healing

by Chiara Rigo, Letizia Ferroni, Ilaria Tocco, Marco Roman, Ivan Munivrana, Chiara Gardin, Warren R. L. Cairns, Vincenzo Vindigni, Bruno Azzena, Carlo Barbante and Barbara Zavan

Int. J. Mol. Sci. 2013, 14(3), 4817-4840; doi:10.3390/ijms14034817

Received: 23 December 2012 / Revised: 5 February 2013 / Accepted: 10 February 2013 / Published: 1 March 2013

Cited by 64 | PDF Full-text (2203 KB) | HTML Full-text | XML Full-text

Abstract

In this preliminary study, the silver nanoparticle (Ag NP)-based dressing, Acticoat™ Flex 3, has been applied to a 3D fibroblast cell culture in vitro and to a real partial thickness burn patient. The in vitro results show that Ag NPs greatly reduce mitochondrial

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In this preliminary study, the silver nanoparticle (Ag NP)-based dressing, Acticoat™ Flex 3, has been applied to a 3D fibroblast cell culture in vitro and to a real partial thickness burn patient. The in vitro results show that Ag NPs greatly reduce mitochondrial activity, while cellular staining techniques show that nuclear integrity is maintained, with no signs of cell death. For the first time, transmission electron microscopy (TEM) and inductively coupled plasma mass spectrometry (ICP-MS) analyses were carried out on skin biopsies taken from a single patient during treatment. The results show that Ag NPs are released as aggregates and are localized in the cytoplasm of fibroblasts. No signs of cell death were observed, and the nanoparticles had different distributions within the cells of the upper and lower dermis. Depth profiles of the Ag concentrations were determined along the skin biopsies. In the healed sample, most of the silver remained in the surface layers, whereas in the unhealed sample, the silver penetrated more deeply. The Ag concentrations in the cell cultures were also determined. Clinical observations and experimental data collected here are consistent with previously published articles and support the safety of Ag NP-based dressing in wound treatment. Full article

Open AccessArticle Preparation of Chitosan and Water-Soluble Chitosan Microspheres via Spray-Drying Method to Lower Blood Lipids in Rats Fed with High-Fat Diets

by Yi Tao, Hong-Liang Zhang, Yin-Ming Hu, Shuo Wan and Zheng-Quan Su

Int. J. Mol. Sci. 2013, 14(2), 4174-4184; doi:10.3390/ijms14024174

Received: 27 November 2012 / Revised: 30 January 2013 / Accepted: 1 February 2013 / Published: 19 February 2013

Cited by 23 | PDF Full-text (1251 KB) | HTML Full-text | XML Full-text

Abstract

This experiment aimed to investigate the effects of the chitosan (CTS) and water-soluble chitosan (WSC) microspheres on plasma lipids in male Sprague-Dawley rats fed with high-fat diets. CTS microspheres and WSC microspheres were prepared by the spray-drying technique. Scanning electron microscopy (SEM) micrographs

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This experiment aimed to investigate the effects of the chitosan (CTS) and water-soluble chitosan (WSC) microspheres on plasma lipids in male Sprague-Dawley rats fed with high-fat diets. CTS microspheres and WSC microspheres were prepared by the spray-drying technique. Scanning electron microscopy (SEM) micrographs showed that the microspheres were nearly spherical in shape. The mean size of CTS microspheres was 4.07 μm (varying from 1.50 to 7.21 μm) and of WSC microspheres was 2.00 μm (varying from 0.85 to 3.58 μm). The rats were classified into eight groups (n = 8) and were fed with high-fat diets for two weeks to establish the hyperlipidemic condition and were then treated with CTS microspheres and WSC microspheres, CTS and WSC for four weeks. The results showed that CTS and WSC microspheres reduced blood lipids and plasma viscosity and increased the serum superoxide dismutase (SOD) levels significantly. This study is the first report of the lipid-lowering effects of CTS and WSC microspheres. CTS and WSC microspheres were found to be more effective in improving hyperlipidemia in rats than common CTS and WSC. Full article

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Open AccessArticle Cytotoxicity and Genotoxicity of Ceria Nanoparticles on Different Cell Lines in Vitro

by Laura De Marzi, Antonina Monaco, Joaquin De Lapuente, David Ramos, Miquel Borras, Mario Di Gioacchino, Sandro Santucci and Anna Poma

Int. J. Mol. Sci. 2013, 14(2), 3065-3077; doi:10.3390/ijms14023065

Received: 29 November 2012 / Revised: 4 January 2013 / Accepted: 21 January 2013 / Published: 1 February 2013

Cited by 31 | PDF Full-text (741 KB) | HTML Full-text | XML Full-text

Abstract

Owing to their radical scavenging and UV-filtering properties, ceria nanoparticles (CeO₂-NPs) are currently used for various applications, including as catalysts in diesel particulate filters. Because of their ability to filter UV light, CeO₂-NPs have garnered significant interest in the

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Owing to their radical scavenging and UV-filtering properties, ceria nanoparticles (CeO₂-NPs) are currently used for various applications, including as catalysts in diesel particulate filters. Because of their ability to filter UV light, CeO₂-NPs have garnered significant interest in the medical field and, consequently, are poised for use in various applications. The aim of this work was to investigate the effects of short-term (24 h) and long-term (10 days) CeO₂-NP exposure to A549, CaCo2 and HepG2 cell lines. Cytotoxicity assays tested CeO₂-NPs over a concentration range of 0.5 μg/mL to 5000 μg/mL, whereas genotoxicity assays tested CeO₂-NPs over a concentration range of 0.5 μg/mL to 5000 μg/mL. In vitro assays showed almost no short-term exposure toxicity on any of the tested cell lines. Conversely, long-term CeO₂-NP exposure proved toxic for all tested cell lines. NP genotoxicity was detectable even at 24-h exposure. HepG2 was the most sensitive cell line overall; however, the A549 line was most sensitive to the lowest concentration tested. Moreover, the results confirmed the ceria nanoparticles’ capacity to protect cells when they are exposed to well-known oxidants such as H₂O₂. A Comet assay was performed in the presence of both H₂O₂ and CeO₂-NPs. When hydrogen peroxide was maintained at 25 μM, NPs at 0.5 μg/mL, 50 μg/mL, and 500 μg/mL protected the cells from oxidative damage. Thus, the NPs prevented H₂O₂-induced genotoxic damage. Full article

Open AccessArticle In Vitro and in Vivo Evaluation of Lactoferrin-Conjugated Liposomes as a Novel Carrier to Improve the Brain Delivery

by Feng-Yun J. Huang, Wan-Jou Chen, Wan-Yu Lee, Su-Tang Lo, Te-Wei Lee and Jem-Mau Lo

Int. J. Mol. Sci. 2013, 14(2), 2862-2874; doi:10.3390/ijms14022862

Received: 19 November 2012 / Revised: 4 January 2013 / Accepted: 22 January 2013 / Published: 29 January 2013

Cited by 30 | PDF Full-text (575 KB) | HTML Full-text | XML Full-text

Abstract

In this study, lactoferrin-conjugated PEGylated liposomes (PL), a potential drug carrier for brain delivery, was loaded with radioisotope complex, ^99mTc labeled N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (^99mTc-BMEDA) for in vitro and in vivo evaluations. The hydrophilicity of

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In this study, lactoferrin-conjugated PEGylated liposomes (PL), a potential drug carrier for brain delivery, was loaded with radioisotope complex, ^99mTc labeled N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (^99mTc-BMEDA) for in vitro and in vivo evaluations. The hydrophilicity of liposomes was enhanced by PEGylation which was not an ideal brain delivery system for crossing the blood brain barrier (BBB). With the modification of a brain-targeting ligand, lactoferrin (Lf), the PEGylated liposome (PL) might become a potential brain delivery vehicle. In order to test the hypothesis in vitro and in vivo, ^99mTc-BMEDA was loaded into the liposomes as a reporter with or without Lf-conjugation. The mouse brain endothelia cell line, bEnd.3 cells, was cultured to investigate the potential uptake of liposomes in vitro. The in vivo uptake by the mouse brain of the liposomes was detected by tissue biodistribution study. The results indicated that Lf-conjugated PEGylated liposome showed more than three times better uptake efficiency in vitro and two-fold higher of brain uptake in vivo than PEGlyated liposome. With the success of loading the potential Single Photon Emission Tomography (SPECT) imaging probe, ^99mTc-BMEDA, Lf-PL might serve as a promising brain delivery system for loading diagnostics or therapeutics of various brain disorders. Full article

Open AccessArticle Comparative in Vivo Assessment of Some Adverse Bioeffects of Equidimensional Gold and Silver Nanoparticles and the Attenuation of Nanosilver’s Effects with a Complex of Innocuous Bioprotectors

Int. J. Mol. Sci. 2013, 14(2), 2449-2483; doi:10.3390/ijms14022449

Received: 9 November 2012 / Revised: 8 January 2013 / Accepted: 9 January 2013 / Published: 25 January 2013

Cited by 25 | PDF Full-text (3970 KB) | HTML Full-text | XML Full-text

Abstract

Stable suspensions of nanogold (NG) and nanosilver (NS) with mean particle diameter 50 and 49 nm, respectively, were prepared by laser ablation of metals in water. To assess rat’s pulmonary phagocytosis response to a single intratracheal instillation of these suspensions, we used optical,

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Stable suspensions of nanogold (NG) and nanosilver (NS) with mean particle diameter 50 and 49 nm, respectively, were prepared by laser ablation of metals in water. To assess rat’s pulmonary phagocytosis response to a single intratracheal instillation of these suspensions, we used optical, transmission electron, and semi-contact atomic force microscopy. NG and NS were also repeatedly injected intraperitoneally into rats at a dose of 10 mg/kg (0.5 mg per mL of deionized water) three times a week, up to 20 injections. A group of rats was thus injected with NS after oral administration of a “bioprotective complex” (BPC) comprised of pectin, multivitamins, some amino acids, calcium, selenium, and omega-3 PUFA. After the termination of the injections, many functional and biochemical indices and histopathological features of the spleen, kidneys and liver were evaluated for signs of toxicity, and accumulation of NG or NS in these organs was measured. From the same rats, we obtained cell suspensions of different tissues for performing the RAPD test. It was demonstrated that, although both nanometals were adversely bioactive in all respects considered in this study, NS was more noxious as compared with NG, and that the BPC tested by us attenuated both the toxicity and genotoxicity of NS. Full article

Open AccessReview Nanostructured Surfaces of Dental Implants

by Eriberto Bressan, Luca Sbricoli, Riccardo Guazzo, Ilaria Tocco, Marco Roman, Vincenzo Vindigni, Edoardo Stellini, Chiara Gardin, Letizia Ferroni, Stefano Sivolella and Barbara Zavan

Int. J. Mol. Sci. 2013, 14(1), 1918-1931; doi:10.3390/ijms14011918

Received: 9 October 2012 / Revised: 21 December 2012 / Accepted: 4 January 2013 / Published: 17 January 2013

Cited by 19 | PDF Full-text (473 KB) | HTML Full-text | XML Full-text

Abstract

The structural and functional fusion of the surface of the dental implant with the surrounding bone (osseointegration) is crucial for the short and long term outcome of the device. In recent years, the enhancement of bone formation at the bone-implant interface has been

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The structural and functional fusion of the surface of the dental implant with the surrounding bone (osseointegration) is crucial for the short and long term outcome of the device. In recent years, the enhancement of bone formation at the bone-implant interface has been achieved through the modulation of osteoblasts adhesion and spreading, induced by structural modifications of the implant surface, particularly at the nanoscale level. In this context, traditional chemical and physical processes find new applications to achieve the best dental implant technology. This review provides an overview of the most common manufacture techniques and the related cells-surface interactions and modulation. A Medline and a hand search were conducted to identify studies concerning nanostructuration of implant surface and their related biological interaction. In this paper, we stressed the importance of the modifications on dental implant surfaces at the nanometric level. Nowadays, there is still little evidence of the long-term benefits of nanofeatures, as the promising results achieved in vitro and in animals have still to be confirmed in humans. However, the increasing interest in nanotechnology is undoubted and more research is going to be published in the coming years. Full article

Open AccessReview Biopolymer-Based Nanoparticles for Drug/Gene Delivery and Tissue Engineering

by Sachiko Kaihara Nitta and Keiji Numata

Int. J. Mol. Sci. 2013, 14(1), 1629-1654; doi:10.3390/ijms14011629

Received: 24 September 2012 / Revised: 27 November 2012 / Accepted: 7 January 2013 / Published: 14 January 2013

Cited by 131 | PDF Full-text (354 KB) | HTML Full-text | XML Full-text

Abstract

There has been a great interest in application of nanoparticles as biomaterials for delivery of therapeutic molecules such as drugs and genes, and for tissue engineering. In particular, biopolymers are suitable materials as nanoparticles for clinical application due to their versatile traits, including

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There has been a great interest in application of nanoparticles as biomaterials for delivery of therapeutic molecules such as drugs and genes, and for tissue engineering. In particular, biopolymers are suitable materials as nanoparticles for clinical application due to their versatile traits, including biocompatibility, biodegradability and low immunogenicity. Biopolymers are polymers that are produced from living organisms, which are classified in three groups: polysaccharides, proteins and nucleic acids. It is important to control particle size, charge, morphology of surface and release rate of loaded molecules to use biopolymer-based nanoparticles as drug/gene delivery carriers. To obtain a nano-carrier for therapeutic purposes, a variety of materials and preparation process has been attempted. This review focuses on fabrication of biocompatible nanoparticles consisting of biopolymers such as protein (silk, collagen, gelatin, β-casein, zein and albumin), protein-mimicked polypeptides and polysaccharides (chitosan, alginate, pullulan, starch and heparin). The effects of the nature of the materials and the fabrication process on the characteristics of the nanoparticles are described. In addition, their application as delivery carriers of therapeutic drugs and genes and biomaterials for tissue engineering are also reviewed. Full article

Open AccessArticle Folate-Equipped Nanolipoplexes Mediated Efficient Gene Transfer into Human Epithelial Cells

by Emmanuel Mornet, Nathalie Carmoy, Céline Lainé, Loïc Lemiègre, Tony Le Gall, Isabelle Laurent, Remi Marianowski, Claude Férec, Pierre Lehn, Thierry Benvegnu and Tristan Montier

Int. J. Mol. Sci. 2013, 14(1), 1477-1501; doi:10.3390/ijms14011477

Received: 10 December 2012 / Revised: 31 December 2012 / Accepted: 6 January 2013 / Published: 14 January 2013

Cited by 11 | PDF Full-text (1914 KB) | HTML Full-text | XML Full-text

Abstract

Since recombinant viral vectors have been associated with serious side effects, such as immunogenicity and oncogenicity, synthetic delivery systems represent a realistic alternative for achieving efficacy in gene therapy. A major challenge for non-viral nanocarriers is the optimization of transgene expression in the

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Since recombinant viral vectors have been associated with serious side effects, such as immunogenicity and oncogenicity, synthetic delivery systems represent a realistic alternative for achieving efficacy in gene therapy. A major challenge for non-viral nanocarriers is the optimization of transgene expression in the targeted cells. This goal can be achieved by fine-tuning the chemical carriers and the adding specific motifs to promote cellular penetration. Our study focuses on the development of novel folate-based complexes that contain varying quantities of folate motifs. After controlling for their physical properties, neutral folate-modified lipid formulations were compared in vitro to lipoplexes leading to comparable expression levels. In addition, no cytotoxicity was detected, unlike what was observed in the cationic controls. Mechanistically, the delivery of the transgene appeared to be, in part, due to endocytosis mediated by folate receptor targeting. This mechanism was further validated by the observation that adding free folate into the medium decreased luciferase expression by 50%. In vivo transfection with the folate-modified MM18 lipid, containing the highest amount of FA-PEG₅₇₀-diether co-lipid (w:w; 90:10), at a neutral charge ratio, gave luciferase transgene expression. These studies indicate that modification of lipids with folate residues could enhance non-toxic, cell-specific gene delivery. Full article

Open AccessArticle Evaluation of Anti-Inflammatory Drug-Conjugated Silicon Quantum Dots: Their Cytotoxicity and Biological Effect

by Sanshiro Hanada, Kouki Fujioka, Yasuhiro Futamura, Noriyoshi Manabe, Akiyoshi Hoshino and Kenji Yamamoto

Int. J. Mol. Sci. 2013, 14(1), 1323-1334; doi:10.3390/ijms14011323

Received: 20 December 2012 / Revised: 1 January 2013 / Accepted: 5 January 2013 / Published: 10 January 2013

Cited by 12 | PDF Full-text (752 KB) | HTML Full-text | XML Full-text

Abstract

Silicon quantum dots (Si-QDs) have great potential for biomedical applications, including their use as biological fluorescent markers and carriers for drug delivery systems. Biologically inert Si-QDs are less toxic than conventional cadmium-based QDs, and can modify the surface of the Si-QD with covalent

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Silicon quantum dots (Si-QDs) have great potential for biomedical applications, including their use as biological fluorescent markers and carriers for drug delivery systems. Biologically inert Si-QDs are less toxic than conventional cadmium-based QDs, and can modify the surface of the Si-QD with covalent bond. We synthesized water-soluble alminoprofen-conjugated Si-QDs (Ap-Si). Alminoprofen is a non-steroid anti-inflammatory drug (NSAID) used as an analgesic for rheumatism. Our results showed that the “silicon drug” is less toxic than the control Si-QD and the original drug. These phenomena indicate that the condensed surface integration of ligand/receptor-type drugs might reduce the adverse interaction between the cells and drug molecules. In addition, the medicinal effect of the Si-QDs (i.e., the inhibition of COX-2 enzyme) was maintained compared to that of the original drug. The same drug effect is related to the integration ratio of original drugs, which might control the binding interaction between COX-2 and the silicon drug. We conclude that drug conjugation with biocompatible Si-QDs is a potential method for functional pharmaceutical drug development. Full article

Open AccessArticle In Vitro Cytotoxicity of Fluorescent Silica Nanoparticles Hybridized with Aggregation-Induced Emission Luminogens for Living Cell Imaging

by Yun Xia, Min Li, Tao Peng, Weijie Zhang, Jun Xiong, Qinggang Hu, Zifang Song and Qichang Zheng

Int. J. Mol. Sci. 2013, 14(1), 1080-1092; doi:10.3390/ijms14011080

Received: 21 November 2012 / Revised: 28 December 2012 / Accepted: 28 December 2012 / Published: 7 January 2013

Cited by 6 | PDF Full-text (1917 KB) | HTML Full-text | XML Full-text

Abstract

Fluorescent silica nanoparticles (FSNPs) can provide high-intensity and photostable fluorescent signals as a probe for biomedical analysis. In this study, FSNPs hybridized with aggregation-induced emission (AIE) luminogens (namely FSNP-SD) were successfully fabricated by a surfactant-free sol-gel method. The FSNP-SD were spherical, monodisperse and

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Fluorescent silica nanoparticles (FSNPs) can provide high-intensity and photostable fluorescent signals as a probe for biomedical analysis. In this study, FSNPs hybridized with aggregation-induced emission (AIE) luminogens (namely FSNP-SD) were successfully fabricated by a surfactant-free sol-gel method. The FSNP-SD were spherical, monodisperse and uniform in size, with an average diameter of approximately 100 nm, and emitted strong fluorescence at the peak of 490 nm. The FSNP-SD selectively stained the cytoplasmic regions and were distributed in the cytoplasm. Moreover, they can stay inside cells, enabling the tacking of cells over a long period of time. The intracellular vesicles and multinucleated cells were increase gradually with the rise of FSNP-SD concentration. Both cell viability and survival only lost less than 20% when the cells were exposed to the high concentration of 100 μg/mL FSNP-SD. Additionally, the cell apoptosis and intracellular ROS assay indicated that FSNP-SD had no significant toxic effects at the maximum working concentration of 80 μg/mL. This study demonstrated that the FSNP-SD are promising biocompatible fluorescent probes for living cell imaging. Full article

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Open AccessReview Intelligent Design of Nano-Scale Molecular Imaging Agents

by Sung Bae Kim, Mitsuru Hattori and Takeaki Ozawa

Int. J. Mol. Sci. 2012, 13(12), 16986-17005; doi:10.3390/ijms131216986

Received: 21 September 2012 / Accepted: 26 November 2012 / Published: 12 December 2012

Cited by 5 | PDF Full-text (792 KB) | HTML Full-text | XML Full-text

Abstract

Visual representation and quantification of biological processes at the cellular and subcellular levels within living subjects are gaining great interest in life science to address frontier issues in pathology and physiology. As intact living subjects do not emit any optical signature, visual representation

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Visual representation and quantification of biological processes at the cellular and subcellular levels within living subjects are gaining great interest in life science to address frontier issues in pathology and physiology. As intact living subjects do not emit any optical signature, visual representation usually exploits nano-scale imaging agents as the source of image contrast. Many imaging agents have been developed for this purpose, some of which exert nonspecific, passive, and physical interaction with a target. Current research interest in molecular imaging has mainly shifted to fabrication of smartly integrated, specific, and versatile agents that emit fluorescence or luminescence as an optical readout. These agents include luminescent quantum dots (QDs), biofunctional antibodies, and multifunctional nanoparticles. Furthermore, genetically encoded nano-imaging agents embedding fluorescent proteins or luciferases are now gaining popularity. These agents are generated by integrative design of the components, such as luciferase, flexible linker, and receptor to exert a specific on–off switching in the complex context of living subjects. In the present review, we provide an overview of the basic concepts, smart design, and practical contribution of recent nano-scale imaging agents, especially with respect to genetically encoded imaging agents. Full article

Open AccessArticle Photodegradable Polyesters for Triggered Release

by Cong Lv, Zhen Wang, Peng Wang and Xinjing Tang

Int. J. Mol. Sci. 2012, 13(12), 16387-16399; doi:10.3390/ijms131216387

Received: 28 September 2012 / Revised: 14 November 2012 / Accepted: 16 November 2012 / Published: 3 December 2012

Cited by 8 | PDF Full-text (929 KB) | HTML Full-text | XML Full-text | Supplementary Files

Abstract

Photodegradable polyesters were synthesized with a photolabile monomer 2-nitrophenylethylene glycol and dioyl chlorides with different lengths. These polymers can be assembled to form polymeric particles with encapsulation of target substances. Light activation can degrade these particles and release payloads in both aqueous solutions

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Photodegradable polyesters were synthesized with a photolabile monomer 2-nitrophenylethylene glycol and dioyl chlorides with different lengths. These polymers can be assembled to form polymeric particles with encapsulation of target substances. Light activation can degrade these particles and release payloads in both aqueous solutions and RAW 264.7 cells. Full article

Open AccessArticle Impairment of Coronary Arteriolar Endothelium-Dependent Dilation after Multi-Walled Carbon Nanotube Inhalation: A Time-Course Study

by Phoebe A. Stapleton, Valerie C. Minarchick, Amy M. Cumpston, Walter McKinney, Bean T. Chen, Tina M. Sager, David G. Frazer, Robert R. Mercer, James Scabilloni, Michael E. Andrew, Vincent Castranova and Timothy R. Nurkiewicz

Int. J. Mol. Sci. 2012, 13(11), 13781-13803; doi:10.3390/ijms131113781

Received: 17 September 2012 / Revised: 12 October 2012 / Accepted: 16 October 2012 / Published: 24 October 2012

Cited by 42 | PDF Full-text (3098 KB) | HTML Full-text | XML Full-text

Abstract

Engineered nanomaterials have been developed for widespread applications due to many highly unique and desirable characteristics. The purpose of this study was to assess pulmonary inflammation and subepicardial arteriolar reactivity in response to multi-walled carbon nanotube (MWCNT) inhalation and evaluate the time course

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Engineered nanomaterials have been developed for widespread applications due to many highly unique and desirable characteristics. The purpose of this study was to assess pulmonary inflammation and subepicardial arteriolar reactivity in response to multi-walled carbon nanotube (MWCNT) inhalation and evaluate the time course of vascular alterations. Rats were exposed to MWCNT aerosols producing pulmonary deposition. Pulmonary inflammation via bronchoalveolar lavage and MWCNT translocation from the lungs to systemic organs was evident 24 h post-inhalation. Coronary arterioles were evaluated 24–168 h post-exposure to determine microvascular response to changes in transmural pressure, endothelium-dependent and -independent reactivity. Myogenic responsiveness, vascular smooth muscle reactivity to nitric oxide, and α-adrenergic responses all remained intact. However, a severe impact on endothelium-dependent dilation was observed within 24 h after MWCNT inhalation, a condition which improved, but did not fully return to control after 168 h. In conclusion, results indicate that MWCNT inhalation not only leads to pulmonary inflammation and cytotoxicity at low lung burdens, but also a low level of particle translocation to systemic organs. MWCNT inhalation also leads to impairments of endothelium-dependent dilation in the coronary microcirculation within 24 h, a condition which does not fully dissipate within 168 h. The innovations within the field of nanotechnology, while exciting and novel, can only reach their full potential if toxicity is first properly assessed. Full article

Open AccessArticle Cytotoxicity of Phenol Red in Toxicity Assays for Carbon Nanoparticles

by Ying Zhu, Xiaoyong Zhang, Jianhua Zhu, Qunfen Zhao, Yuguo Li, Wenxin Li, Chunhai Fan and Qing Huang

Int. J. Mol. Sci. 2012, 13(10), 12336-12348; doi:10.3390/ijms131012336

Received: 16 August 2012 / Revised: 18 September 2012 / Accepted: 19 September 2012 / Published: 26 September 2012

Cited by 22 | PDF Full-text (852 KB) | HTML Full-text | XML Full-text | Supplementary Files

Abstract

To explore the novel properties of carbon nanoparticles (CNPs) in nanotoxicity assays, the adsorption of phenol red (a pH indicator for culture medium) by multi-walled carbon nanotubes (MWNTs) and three kinds of carbon blacks (CBs) with nanosize, and its effects on cytotoxicity were

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To explore the novel properties of carbon nanoparticles (CNPs) in nanotoxicity assays, the adsorption of phenol red (a pH indicator for culture medium) by multi-walled carbon nanotubes (MWNTs) and three kinds of carbon blacks (CBs) with nanosize, and its effects on cytotoxicity were studied. Results indicated that the phenol red adsorbed and delivered into cells by CBs was responsible for the toxicity to Hela cells in the medium without serum. The cellular uptake of phenol red was verified using ¹²⁵I-labeling techniques. The size-dependent cytotoxicity of CBs was found to closely correlate to adsorption of phenol red, cellular uptake of phenol red-CB complexes and the amount of phenol red delivered into the cells by CBs. Although the CBs were either nontoxic or slightly toxic, as vehicles of phenol red, they played an essential role in the cytotoxicity induced by phenol red. However, MWNTs showed an intrinsic cytotoxicity independent of phenol red. The implications associated with these findings are discussed. Full article

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Open AccessArticle Cellular Delivery of Doxorubicin via pH-Controlled Hydrazone Linkage Using Multifunctional Nano Vehicle Based on Poly(β-L-Malic Acid)

by Rameshwar Patil, Jose Portilla-Arias, Hui Ding, Bindu Konda, Arthur Rekechenetskiy, Satoshi Inoue, Keith L. Black, Eggehard Holler and Julia Y. Ljubimova

Int. J. Mol. Sci. 2012, 13(9), 11681-11693; doi:10.3390/ijms130911681

Received: 12 July 2012 / Revised: 17 August 2012 / Accepted: 7 September 2012 / Published: 17 September 2012

Cited by 28 | PDF Full-text (813 KB) | HTML Full-text | XML Full-text

Abstract

Doxorubicin (DOX) is currently used in cancer chemotherapy to treat many tumors and shows improved delivery, reduced toxicity and higher treatment efficacy when being part of nanoscale delivery systems. However, a major drawback remains its toxicity to healthy tissue and the development of

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Doxorubicin (DOX) is currently used in cancer chemotherapy to treat many tumors and shows improved delivery, reduced toxicity and higher treatment efficacy when being part of nanoscale delivery systems. However, a major drawback remains its toxicity to healthy tissue and the development of multi-drug resistance during prolonged treatment. This is why in our work we aimed to improve DOX delivery and reduce the toxicity by chemical conjugation with a new nanoplatform based on polymalic acid. For delivery into recipient cancer cells, DOX was conjugated via pH-sensitive hydrazone linkage along with polyethylene glycol (PEG) to a biodegradable, non-toxic and non-immunogenic nanoconjugate platform: poly(β-L-malic acid) (PMLA). DOX-nanoconjugates were found stable under physiological conditions and shown to successfully inhibit in vitro cancer cell growth of several invasive breast carcinoma cell lines such as MDA-MB-231 and MDA-MB- 468 and of primary glioma cell lines such as U87MG and U251. Full article

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Open AccessReview Vectors for Inhaled Gene Therapy in Lung Cancer. Application for Nano Oncology and Safety of Bio Nanotechnology

by Paul Zarogouldis, Nikos K. Karamanos, Konstantinos Porpodis, Kalliopi Domvri, Haidong Huang, Wolfgang Hohenforst-Schimdt, Eugene P. Goldberg and Konstantinos Zarogoulidis

Int. J. Mol. Sci. 2012, 13(9), 10828-10862; doi:10.3390/ijms130910828

Received: 30 July 2012 / Revised: 21 August 2012 / Accepted: 22 August 2012 / Published: 29 August 2012

Cited by 19 | PDF Full-text (841 KB) | HTML Full-text | XML Full-text | Supplementary Files

Abstract

Novel aerosol therapeutic modalities have been investigated for lung cancer. Inhaled gene therapy has presented safety and effectiveness previously in cystic fibrosis. However, safety concerns have been raised regarding the safety of non-viral vectors for inhaled gene therapy in lung cancer, and therefore

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Novel aerosol therapeutic modalities have been investigated for lung cancer. Inhaled gene therapy has presented safety and effectiveness previously in cystic fibrosis. However, safety concerns have been raised regarding the safety of non-viral vectors for inhaled gene therapy in lung cancer, and therefore small steps have been made towards this multifunctional treatment modality. During the last decade, numerous new nanocomplexes have been created and investigated as a safe gene delivery nano-vehicle. These formulations are multifunctional; they can be used as either local therapy or carrier for an effective inhaled gene therapy for lung cancer. Herein, we present current and future perspectives of nanocomplexes for inhaled gene therapy treatment in lung cancer. Full article

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Open AccessArticle Structural and Oxidative Changes in the Kidney of Crucian Carp Induced by Silicon-Based Quantum Dots

by Sorina Nicoleta Petrache, Loredana Stanca, Andreea Iren Serban, Cornelia Sima, Andreia Cristina Staicu, Maria Cristina Munteanu, Marieta Costache, Radu Burlacu, Otilia Zarnescu and Anca Dinischiotu

Int. J. Mol. Sci. 2012, 13(8), 10193-10211; doi:10.3390/ijms130810193

Received: 2 July 2012 / Revised: 28 July 2012 / Accepted: 9 August 2012 / Published: 16 August 2012

Cited by 9 | PDF Full-text (419 KB) | HTML Full-text | XML Full-text

Abstract

Silicon-based quantum dots were intraperitoneally injected in Carassius auratus gibelio specimens and, over one week, the effects on renal tissue were investigated by following their distribution and histological effects, as well as antioxidative system modifications. After three and seven days, detached epithelial cells

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Silicon-based quantum dots were intraperitoneally injected in Carassius auratus gibelio specimens and, over one week, the effects on renal tissue were investigated by following their distribution and histological effects, as well as antioxidative system modifications. After three and seven days, detached epithelial cells from the basal lamina, dilated tubules and debris in the lumen of tubules were observed. At day 7, nephrogenesis was noticed. The reduced glutathione (GSH) concentration decreased in the first three days and started to rise later on. The superoxide dismutase (SOD) activity increased only after one week, whereas catalase (CAT) was up-regulated in a time-dependent manner. The activities of glutathione reductase (GR) and glutathione peroxidise (GPX) decreased dramatically by approximately 50% compared to control, whereas the glutathione-S-transferase (GST) and glucose-6-phosphate dehydrogenase (G6PDH) increased significantly after 3 and 7 days of treatment. Oxidative modifications of proteins and the time-dependent increase of Hsp70 expression were also registered. Our data suggest that silicon-based quantum dots induced oxidative stress followed by structural damages. However, renal tissue is capable of restoring its integrity by nephron development. Full article

Open AccessArticle Green Synthesis of Silver Nanoparticles through Reduction with Solanum xanthocarpum L. Berry Extract: Characterization, Antimicrobial and Urease Inhibitory Activities against Helicobacter pylori

by Muhammad Amin, Farooq Anwar, Muhammad Ramzan Saeed Ashraf Janjua, Muhammad Awais Iqbal and Umer Rashid

Int. J. Mol. Sci. 2012, 13(8), 9923-9941; doi:10.3390/ijms13089923

Received: 1 June 2012 / Revised: 23 July 2012 / Accepted: 25 July 2012 / Published: 9 August 2012

Cited by 76 | PDF Full-text (565 KB) | HTML Full-text | XML Full-text

Abstract

A green synthesis route for the production of silver nanoparticles using methanol extract from Solanum xanthocarpum berry (SXE) is reported in the present investigation. Silver nanoparticles (AgNps), having a surface plasmon resonance (SPR) band centered at 406 nm, were synthesized by reacting SXE

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A green synthesis route for the production of silver nanoparticles using methanol extract from Solanum xanthocarpum berry (SXE) is reported in the present investigation. Silver nanoparticles (AgNps), having a surface plasmon resonance (SPR) band centered at 406 nm, were synthesized by reacting SXE (as capping as well as reducing agent) with AgNO₃ during a 25 min process at 45 °C. The synthesized AgNps were characterized using UV–Visible spectrophotometry, powdered X-ray diffraction, and transmission electron microscopy (TEM). The results showed that the time of reaction, temperature and volume ratio of SXE to AgNO₃ could accelerate the reduction rate of Ag⁺ and affect the AgNps size and shape. The nanoparticles were found to be about 10 nm in size, mono-dispersed in nature, and spherical in shape. In vitro anti-Helicobacter pylori activity of synthesized AgNps was tested against 34 clinical isolates and two reference strains of Helicobacter pylori by the agar dilution method and compared with AgNO₃ and four standard drugs, namely amoxicillin (AMX), clarithromycin (CLA), metronidazole (MNZ) and tetracycline (TET), being used in anti-H. pylori therapy. Typical AgNps sample (S1) effectively inhibited the growth of H. pylori, indicating a stronger anti-H. pylori activity than that of AgNO₃ or MNZ, being almost equally potent to TET and less potent than AMX and CLA. AgNps under study were found to be equally efficient against the antibiotic-resistant and antibiotic-susceptible strains of H. pylori. Besides, in the H. pylori urease inhibitory assay, S1 also exhibited a significant inhibition. Lineweaver-Burk plots revealed that the mechanism of inhibition was noncompetitive. Full article

Open AccessReview Antioxidant-Induced Stress

by Cleva Villanueva and Robert D. Kross

Int. J. Mol. Sci. 2012, 13(2), 2091-2109; doi:10.3390/ijms13022091

Received: 19 December 2011 / Revised: 30 January 2012 / Accepted: 13 February 2012 / Published: 16 February 2012

Cited by 37 | PDF Full-text (357 KB) | HTML Full-text | XML Full-text

Abstract

Antioxidants are among the most popular health-protecting products, sold worldwide without prescription. Indeed, there are many reports showing the benefits of antioxidants but only a few questioning the possible harmful effects of these “drugs”. The normal balance between antioxidants and free radicals in

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Antioxidants are among the most popular health-protecting products, sold worldwide without prescription. Indeed, there are many reports showing the benefits of antioxidants but only a few questioning the possible harmful effects of these “drugs”. The normal balance between antioxidants and free radicals in the body is offset when either of these forces prevails. The available evidence on the harmful effects of antioxidants is analyzed in this review. In summary, a hypothesis is presented that “antioxidant-induced stress” results when antioxidants overwhelm the body’s free radicals. Full article

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2011

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Open AccessArticle Fabrication, Modeling and Characterization of Multi-Crosslinked Methacrylate Copolymeric Nanoparticles for Oral Drug Delivery

by Ndidi C. Ngwuluka, Viness Pillay, Yahya E. Choonara, Girish Modi, Dinesh Naidoo, Lisa C. du Toit, Pradeep Kumar, Valence M.K. Ndesendo and Riaz A. Khan

Int. J. Mol. Sci. 2011, 12(9), 6194-6225; doi:10.3390/ijms12096194

Received: 27 July 2011 / Accepted: 4 August 2011 / Published: 23 September 2011

Cited by 9 | PDF Full-text (2625 KB) | HTML Full-text | XML Full-text

Abstract

Nanotechnology remains the field to explore in the quest to enhance therapeutic efficacies of existing drugs. Fabrication of a methacrylate copolymer-lipid nanoparticulate (MCN) system was explored in this study for oral drug delivery of levodopa. The nanoparticles were fabricated employing multicrosslinking technology and

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Nanotechnology remains the field to explore in the quest to enhance therapeutic efficacies of existing drugs. Fabrication of a methacrylate copolymer-lipid nanoparticulate (MCN) system was explored in this study for oral drug delivery of levodopa. The nanoparticles were fabricated employing multicrosslinking technology and characterized for particle size, zeta potential, morphology, structural modification, drug entrapment efficiency and in vitro drug release. Chemometric Computational (CC) modeling was conducted to deduce the mechanism of nanoparticle synthesis as well as to corroborate the experimental findings. The CC modeling deduced that the nanoparticles synthesis may have followed the mixed triangular formations or the mixed patterns. They were found to be hollow nanocapsules with a size ranging from 152 nm (methacrylate copolymer) to 321 nm (methacrylate copolymer blend) and a zeta potential range of 15.8–43.3 mV. The nanoparticles were directly compressible and it was found that the desired rate of drug release could be achieved by formulating the nanoparticles as a nanosuspension, and then directly compressing them into tablet matrices or incorporating the nanoparticles directly into polymer tablet matrices. However, sustained release of MCNs was achieved only when it was incorporated into a polymer matrix. The experimental results were well corroborated by the CC modeling. The developed technology may be potentially useful for the fabrication of multi-crosslinked polymer blend nanoparticles for oral drug delivery. Full article

Open AccessArticle Interaction of Human Serum Album and C₆₀ Aggregates in Solution

by Maoyong Song, Shufang Liu, Junfa Yin and Hailin Wang

Int. J. Mol. Sci. 2011, 12(8), 4964-4974; doi:10.3390/ijms12084964

Received: 30 March 2011 / Revised: 12 July 2011 / Accepted: 27 July 2011 / Published: 4 August 2011

Cited by 22 | PDF Full-text (533 KB) | HTML Full-text | XML Full-text

Abstract

An important property of C₆₀ in aquatic ecotoxicology is that it can form stable aggregates with nanoscale dimensions, namely nC₆₀. Aggregation allows fullerenes to remain suspended for a long time, and the reactivity of individual C₆₀ is substantially altered

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An important property of C₆₀ in aquatic ecotoxicology is that it can form stable aggregates with nanoscale dimensions, namely nC₆₀. Aggregation allows fullerenes to remain suspended for a long time, and the reactivity of individual C₆₀ is substantially altered in this aggregate form. Herein, we investigated the interaction of nC₆₀ and human serum album (HSA) using the methods of fluorescence, fluorescence dynamics, circular dichroism (CD), and site marker competitive experiments. We proposed a binding model consistent with the available experimental results for the interactions of nC₆₀ with HSA. During the interaction process, the structure and conformation of HSA were affected, leading to functional changes of drug binding sites of HSA. Full article

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Open AccessArticle Enhanced Anti-Tumoral Activity of Methotrexate-Human Serum Albumin Conjugated Nanoparticles by Targeting with Luteinizing Hormone-Releasing Hormone (LHRH) Peptide

by Azade Taheri, Rassoul Dinarvand, Fatemeh Atyabi, Fatemeh Ahadi, Farank Salman Nouri, Mohammad Hossein Ghahremani, Seyed Nasser Ostad, Atefeh Taheri Borougeni and Pooria Mansoori

Int. J. Mol. Sci. 2011, 12(7), 4591-4608; doi:10.3390/ijms12074591

Received: 22 May 2011 / Revised: 20 June 2011 / Accepted: 30 June 2011 / Published: 15 July 2011

Cited by 26 | PDF Full-text (685 KB) | HTML Full-text | XML Full-text

Abstract

Active targeting could increase the efficacy of anticancer drugs. Methotrexate-human serum albumin (MTX-HSA) conjugates, functionalized by luteinizing hormone-releasing hormone (LHRH) as targeting moieties, with the aim of specifically targeting the cancer cells, were prepared. Owing to the high expression of LHRH receptors in

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Active targeting could increase the efficacy of anticancer drugs. Methotrexate-human serum albumin (MTX-HSA) conjugates, functionalized by luteinizing hormone-releasing hormone (LHRH) as targeting moieties, with the aim of specifically targeting the cancer cells, were prepared. Owing to the high expression of LHRH receptors in many cancer cells as compared to normal cells, LHRH was used as the targeting ligand in this study. LHRH was conjugated to MTX-HSA nanoparticles via a cross-linker. Three types of LHRH targeted nanoparticles with a mean particle size between 120–138 nm were prepared. The cytotoxicity of LHRH targeted and non-targeted nanoparticles were determined on the LHRH positive and negative cell lines. The internalization of the targeted and non-targeted nanoparticles in LHRH receptor positive and negative cells was investigated using flow cytometry analysis and fluorescence microscopy. The cytotoxicity of the LHRH targeted nanoparticles on the LHRH receptor positive cells were significantly more than non-targeted nanoparticles. LHRH targeted nanoparticles were also internalized by LHRH receptor positive cells significantly more than non-targeted nanoparticles. There were no significant differences between the uptake of targeted and non-targeted nanoparticles to the LHRH receptor negative cells. The active targeting procedure using LHRH targeted MTX-HSA nanoparticles could increase the anti-tumoral activity of MTX. Full article

Open AccessReview Enabling Anticancer Therapeutics by Nanoparticle Carriers: The Delivery of Paclitaxel

by Yongjin Liu, Bin Zhang and Bing Yan

Int. J. Mol. Sci. 2011, 12(7), 4395-4413; doi:10.3390/ijms12074395

Received: 27 April 2011 / Revised: 9 June 2011 / Accepted: 15 June 2011 / Published: 7 July 2011

Cited by 32 | PDF Full-text (468 KB) | HTML Full-text | XML Full-text

Abstract

Anticancer drugs, such as paclitaxel (PTX), are indispensable for the treatment of a variety of malignancies. However, the application of most drugs is greatly limited by the low water solubility, poor permeability, or high efflux from cells. Nanoparticles have been widely investigated to

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Anticancer drugs, such as paclitaxel (PTX), are indispensable for the treatment of a variety of malignancies. However, the application of most drugs is greatly limited by the low water solubility, poor permeability, or high efflux from cells. Nanoparticles have been widely investigated to enable drug delivery due to their low toxicity, sustained drug release, molecular targeting, and additional therapeutic and imaging functions. This review takes paclitaxel as an example and compares different nanoparticle-based delivery systems for their effectiveness in cancer chemotherapy. Full article

Open AccessArticle A Novel Preparation Method for Camptothecin (CPT) Loaded Folic Acid Conjugated Dextran Tumor-Targeted Nanoparticles

by Yuangang Zu, Dan Wang, Xiuhua Zhao, Ru Jiang, Qi Zhang, Dongmei Zhao, Yong Li, Baishi Zu and Zhiqiang Sun

Int. J. Mol. Sci. 2011, 12(7), 4237-4249; doi:10.3390/ijms12074237

Received: 31 March 2011 / Revised: 2 June 2011 / Accepted: 21 June 2011 / Published: 28 June 2011

Cited by 16 | PDF Full-text (486 KB) | HTML Full-text | XML Full-text

Abstract

In this study, folic-dextran-camptothecin (Fa-DEX-CPT) tumor-targeted nanoparticles were produced with a supercritical antisolvent (SAS) technique by using dimethyl sulfoxide (DMSO) as a solvent and carbon dioxide as an antisolvent. A factorial design was used to reveal the effect of various process parameters on

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In this study, folic-dextran-camptothecin (Fa-DEX-CPT) tumor-targeted nanoparticles were produced with a supercritical antisolvent (SAS) technique by using dimethyl sulfoxide (DMSO) as a solvent and carbon dioxide as an antisolvent. A factorial design was used to reveal the effect of various process parameters on the mean particle size (MPS) and morphology of the particles formed. Under the optimum operation conditions, Fa-DEX-CPT nanoparticles with a MPS of 182.21 nm were obtained. Drug encapsulation efficiency and loading efficiency were 62.13% and 36.12%, respectively. It was found that the concentrations of the camptothecin (CPT) and dextran solution had a major influence upon morphology and shape of the final product. In addition, the samples were characterized by Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) with the purpose of developing a suitable targeted drug delivery system for cancer chemotherapy. Full article

Open AccessReview Inorganic-Organic Hybrid Nanomaterials for Therapeutic and Diagnostic Imaging Applications

by Juan L. Vivero-Escoto and Yu-Tzu Huang

Int. J. Mol. Sci. 2011, 12(6), 3888-3927; doi:10.3390/ijms12063888

Received: 11 April 2011 / Accepted: 31 May 2011 / Published: 10 June 2011

Cited by 32 | PDF Full-text (1069 KB) | HTML Full-text | XML Full-text

Abstract

Nanotechnology offers outstanding potential for future biomedical applications. In particular, due to their unique characteristics, hybrid nanomaterials have recently been investigated as promising platforms for imaging and therapeutic applications. This class of nanoparticles can not only retain valuable features of both inorganic and

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Nanotechnology offers outstanding potential for future biomedical applications. In particular, due to their unique characteristics, hybrid nanomaterials have recently been investigated as promising platforms for imaging and therapeutic applications. This class of nanoparticles can not only retain valuable features of both inorganic and organic moieties, but also provides the ability to systematically modify the properties of the hybrid material through the combination of functional elements. Moreover, the conjugation of targeting moieties on the surface of these nanomaterials gives them specific targeted imaging and therapeutic properties. In this review, we summarize the recent reports in the synthesis of hybrid nanomaterials and their applications in biomedical areas. Their applications as imaging and therapeutic agents in vivo will be highlighted. Full article

Open AccessReview Application of Magnetic Nanoparticles to Gene Delivery

by Daisuke Kami, Shogo Takeda, Yoko Itakura, Satoshi Gojo, Masatoshi Watanabe and Masashi Toyoda

Int. J. Mol. Sci. 2011, 12(6), 3705-3722; doi:10.3390/ijms12063705

Received: 6 May 2011 / Revised: 18 May 2011 / Accepted: 25 May 2011 / Published: 7 June 2011

Cited by 57 | PDF Full-text (623 KB) | HTML Full-text | XML Full-text

Abstract

Nanoparticle technology is being incorporated into many areas of molecular science and biomedicine. Because nanoparticles are small enough to enter almost all areas of the body, including the circulatory system and cells, they have been and continue to be exploited for basic biomedical

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Nanoparticle technology is being incorporated into many areas of molecular science and biomedicine. Because nanoparticles are small enough to enter almost all areas of the body, including the circulatory system and cells, they have been and continue to be exploited for basic biomedical research as well as clinical diagnostic and therapeutic applications. For example, nanoparticles hold great promise for enabling gene therapy to reach its full potential by facilitating targeted delivery of DNA into tissues and cells. Substantial progress has been made in binding DNA to nanoparticles and controlling the behavior of these complexes. In this article, we review research on binding DNAs to nanoparticles as well as our latest study on non-viral gene delivery using polyethylenimine-coated magnetic nanoparticles. Full article

Open AccessReview Nanomedicine: Application Areas and Development Prospects

by Houria Boulaiz, Pablo J. Alvarez, Alberto Ramirez, Juan A. Marchal, Jose Prados, Fernando Rodríguez-Serrano, Macarena Perán, Consolación Melguizo and Antonia Aranega

Int. J. Mol. Sci. 2011, 12(5), 3303-3321; doi:10.3390/ijms12053303

Received: 31 March 2011 / Revised: 6 May 2011 / Accepted: 16 May 2011 / Published: 19 May 2011

Cited by 31 | PDF Full-text (402 KB) | HTML Full-text | XML Full-text

Abstract

Nanotechnology, along with related concepts such as nanomaterials, nanostructures and nanoparticles, has become a priority area for scientific research and technological development. Nanotechnology, i.e., the creation and utilization of materials and devices at nanometer scale, already has multiple applications in electronics and

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Nanotechnology, along with related concepts such as nanomaterials, nanostructures and nanoparticles, has become a priority area for scientific research and technological development. Nanotechnology, i.e., the creation and utilization of materials and devices at nanometer scale, already has multiple applications in electronics and other fields. However, the greatest expectations are for its application in biotechnology and health, with the direct impact these could have on the quality of health in future societies. The emerging discipline of nanomedicine brings nanotechnology and medicine together in order to develop novel therapies and improve existing treatments. In nanomedicine, atoms and molecules are manipulated to produce nanostructures of the same size as biomolecules for interaction with human cells. This procedure offers a range of new solutions for diagnoses and “smart” treatments by stimulating the body’s own repair mechanisms. It will enhance the early diagnosis and treatment of diseases such as cancer, diabetes, Alzheimer’s, Parkinson’s and cardiovascular diseases. Preventive medicine may then become a reality. Full article

Open AccessArticle Release of Bacteriocins from Nanofibers Prepared with Combinations of Poly(D,L-lactide) (PDLLA) and Poly(Ethylene Oxide) (PEO)

by Tiaan Heunis, Osama Bshena, Bert Klumperman and Leon Dicks

Int. J. Mol. Sci. 2011, 12(4), 2158-2173; doi:10.3390/ijms12042158

Received: 27 January 2011 / Revised: 24 February 2011 / Accepted: 16 March 2011 / Published: 29 March 2011

Cited by 33 | PDF Full-text (1157 KB) | HTML Full-text | XML Full-text

Abstract

Plantaricin 423, produced by Lactobacillus plantarum, and bacteriocin ST4SA produced by Enterococcus mundtii, were electrospun into nanofibers prepared from different combinations of poly(D,L-lactide) (PDLLA) and poly(ethylene oxide) (PEO) dissolved in N,N-dimethylformamide (DMF). Both peptides were released from the

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Plantaricin 423, produced by Lactobacillus plantarum, and bacteriocin ST4SA produced by Enterococcus mundtii, were electrospun into nanofibers prepared from different combinations of poly(D,L-lactide) (PDLLA) and poly(ethylene oxide) (PEO) dissolved in N,N-dimethylformamide (DMF). Both peptides were released from the nanofibers with a high initial burst and retained 88% of their original antimicrobial activity at 37 °C. Nanofibers have the potential to serve as carrier matrix for bacteriocins and open a new field in developing controlled antimicrobial delivery systems for various applications. Full article

2009

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Open AccessReview Regulation of Enzyme Activity through Interactions with Nanoparticles

by Zhaochun Wu, Bin Zhang and Bing Yan

Int. J. Mol. Sci. 2009, 10(10), 4198-4209; doi:10.3390/ijms10104198

Received: 18 August 2009 / Revised: 15 September 2009 / Accepted: 21 September 2009 / Published: 28 September 2009

Cited by 51 | PDF Full-text (278 KB) | HTML Full-text | XML Full-text

Abstract

The structure and function of an enzyme can be altered by nanoparticles (NPs). The interaction between enzyme and NPs is governed by the key properties of NPs, such as structure, size, surface chemistry, charge and surface shape. Recent representative studies on the NP-enzyme

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The structure and function of an enzyme can be altered by nanoparticles (NPs). The interaction between enzyme and NPs is governed by the key properties of NPs, such as structure, size, surface chemistry, charge and surface shape. Recent representative studies on the NP-enzyme interactions and the regulation of enzyme activity by NPs with different size, composition and surface modification are reviewed. Full article

Open AccessArticle Microscopic Investigation of Reversible Nanoscale Surface Size Dependent Protein Conjugation

by Kazushige Yokoyama, Hyunah Cho, Sean P. Cullen, Matthew Kowalik, Nicole M. Briglio, Harold J. Hoops, Zhouying Zhao and Michael A. Carpenter

Int. J. Mol. Sci. 2009, 10(5), 2348-2366; doi:10.3390/ijms10052348

Received: 3 April 2009 / Revised: 14 May 2009 / Accepted: 18 May 2009 / Published: 20 May 2009

Cited by 6 | PDF Full-text (1107 KB) | HTML Full-text | XML Full-text

Abstract

Aβ_1-40 coated 20 nm gold colloidal nanoparticles exhibit a reversible color change as pH is externally altered between pH 4 and 10. This reversible process may contain important information on the initial reversible step reported for the fibrillogenesis of Aβ (a hallmark

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Aβ_1-40 coated 20 nm gold colloidal nanoparticles exhibit a reversible color change as pH is externally altered between pH 4 and 10. This reversible process may contain important information on the initial reversible step reported for the fibrillogenesis of Aβ (a hallmark of Alzheimer’s disease). We examined this reversible color change by microscopic investigations. AFM images on graphite surfaces revealed the morphology of Aβ aggregates with gold colloids. TEM images clearly demonstrate the correspondence between spectroscopic features and conformational changes of the gold colloid. Full article

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Open AccessArticle A Novel Method for the Preparation of Retinoic Acid-Loaded Nanoparticles

by Cesare Errico, Matteo Gazzarri and Federica Chiellini

Int. J. Mol. Sci. 2009, 10(5), 2336-2347; doi:10.3390/ijms10052336

Received: 27 April 2009 / Revised: 14 May 2009 / Accepted: 18 May 2009 / Published: 19 May 2009

Cited by 4 | PDF Full-text (409 KB) | HTML Full-text | XML Full-text

Abstract

The goal of present work was to investigate the use of bioerodible polymeric nanoparticles as carriers of retinoic acid (RA), which is known to induce differentiation of several cell lines into neurons. A novel method, named “Colloidal-Coating”, has been developed for the preparation

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The goal of present work was to investigate the use of bioerodible polymeric nanoparticles as carriers of retinoic acid (RA), which is known to induce differentiation of several cell lines into neurons. A novel method, named “Colloidal-Coating”, has been developed for the preparation of nanoparticles based on a copolymer of maleic anhydride and butyl vinyl ether (VAM41) loaded with RA. Nanoparticles with an average diameter size of 70 nm and good morphology were prepared. The activity of the encapsulated RA was evaluated on SK-N-SH human neuroblastoma cells, which are known to undergo inhibition of proliferation and neuronal differentiation upon treatment with RA. The activity of RA was not affected by the encapsulation and purification processes. Full article

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