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23 pages, 6048 KiB

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; https://doi.org/10.3390/ijms14059182 - 26 Apr 2013

Cited by 29 | Viewed by 9793

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 [...] Read more.

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

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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15 pages, 1858 KiB

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; https://doi.org/10.3390/ijms14047341 - 2 Apr 2013

Cited by 56 | Viewed by 9756

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 [...] Read more.

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

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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16 pages, 219 KiB

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; https://doi.org/10.3390/ijms14047016 - 27 Mar 2013

Cited by 12 | Viewed by 7987

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 [...] Read more.

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

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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24 pages, 2203 KiB

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; https://doi.org/10.3390/ijms14034817 - 1 Mar 2013

Cited by 259 | Viewed by 21327

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 [...] Read more.

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

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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11 pages, 1251 KiB

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; https://doi.org/10.3390/ijms14024174 - 19 Feb 2013

Cited by 55 | Viewed by 10407

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 [...] Read more.

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

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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13 pages, 741 KiB

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; https://doi.org/10.3390/ijms14023065 - 1 Feb 2013

Cited by 158 | Viewed by 10618

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 [...] Read more.

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

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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13 pages, 575 KiB

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; https://doi.org/10.3390/ijms14022862 - 29 Jan 2013

Cited by 81 | Viewed by 9035

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 [...] Read more.

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

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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35 pages, 3970 KiB

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

by Boris A. Katsnelson, Larisa I. Privalova, Vladimir B. Gurvich, Oleg H. Makeyev, Vladimir Ya. Shur, Yakov B. Beikin, Marina P. Sutunkova, Ekaterina P. Kireyeva, Ilzira A. Minigalieva, Nadezhda V. Loginova, Marina S. Vasilyeva, Artem V. Korotkov, Eugene A. Shuman, Larisa A. Vlasova, Ekaterina V. Shishkina, Anastasia E. Tyurnina, Roman V. Kozin, Irene E. Valamina, Svetlana V. Pichugova and Ludmila G. Tulakina

Int. J. Mol. Sci. 2013, 14(2), 2449-2483; https://doi.org/10.3390/ijms14022449 - 25 Jan 2013

Cited by 63 | Viewed by 11413

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, [...] Read more.

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

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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25 pages, 1914 KiB

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; https://doi.org/10.3390/ijms14011477 - 14 Jan 2013

Cited by 20 | Viewed by 8502

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 [...] Read more.

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

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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12 pages, 752 KiB

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; https://doi.org/10.3390/ijms14011323 - 10 Jan 2013

Cited by 25 | Viewed by 8183

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 [...] Read more.

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

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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13 pages, 1917 KiB

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; https://doi.org/10.3390/ijms14011080 - 7 Jan 2013

Cited by 19 | Viewed by 8731

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 [...] Read more.

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

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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13 pages, 929 KiB

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; https://doi.org/10.3390/ijms131216387 - 3 Dec 2012

Cited by 20 | Viewed by 7181

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 [...] Read more.

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

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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23 pages, 3098 KiB

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; https://doi.org/10.3390/ijms131113781 - 24 Oct 2012

Cited by 97 | Viewed by 8471

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 [...] Read more.

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

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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13 pages, 852 KiB

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; https://doi.org/10.3390/ijms131012336 - 26 Sep 2012

Cited by 36 | Viewed by 9471

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 [...] Read more.

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

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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13 pages, 813 KiB

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; https://doi.org/10.3390/ijms130911681 - 17 Sep 2012

Cited by 75 | Viewed by 14532

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 [...] Read more.

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

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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19 pages, 419 KiB

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; https://doi.org/10.3390/ijms130810193 - 16 Aug 2012

Cited by 20 | Viewed by 9489

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 [...] Read more.

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

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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19 pages, 565 KiB

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; https://doi.org/10.3390/ijms13089923 - 9 Aug 2012

Cited by 322 | Viewed by 19629

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 [...] Read more.

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

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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Review

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14 pages, 473 KiB

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; https://doi.org/10.3390/ijms14011918 - 17 Jan 2013

Cited by 58 | Viewed by 13048

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 [...] Read more.

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

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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26 pages, 354 KiB

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; https://doi.org/10.3390/ijms14011629 - 14 Jan 2013

Cited by 584 | Viewed by 28223

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 [...] Read more.

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

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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20 pages, 792 KiB

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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; https://doi.org/10.3390/ijms131216986 - 12 Dec 2012

Cited by 7 | Viewed by 8957

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 [...] Read more.

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

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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35 pages, 841 KiB

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; https://doi.org/10.3390/ijms130910828 - 29 Aug 2012

Cited by 41 | Viewed by 12937 | Correction

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 [...] Read more.

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

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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