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Bioactive Nanoparticles 2014

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Materials Science".

Deadline for manuscript submissions: closed (31 October 2014) | Viewed by 335911

Special Issue Editor

Key Laboratory for Water Quality and Conservation of the Pearl River Delta, Institute of Environmental Research at Greater Bay, Ministry of Education, Guangzhou University, Guangzhou 510006, China
Interests: nanomedicine; nanotoxicology; environmental safety; environmental toxicology; theranostics; imaging; nanoparticle library; nanoparticle modification; surface modification; chemical biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Nanomaterials will potentially play an important role in medicine. Production and applications of nanomaterials in industry are still increasing. Furthermore, there are more than 1,300 marketed nanomaterial-based consumer products. Therefore, how nanomaterials diagnose and treat diseases and how they perturb normal biological systems will become top concerns. In recent years, researchers are actively engaged in such investigations. At the same time, technologies and methods are being developed to make targeted and biocompatible nanoparticles for medicinal and imaging applications. Since we started the Special Issue “Bioactive Nanoparticles”, responses and submissions from researchers have been enormous. As a result, three further Special Issues “Bioactive Nanoparticles” (https://www.mdpi.com/journal/ijms/special _issues/bioactive_nanoparticles), Bioactive Nanoparticles 2012 (https://www.mdpi.com/journal/ijms/special_issues/nanoparticles_2012), and Bioactive Nanoparticles 2013 (https://www.mdpi.com/journal/ijms/special_issues/bioactive_nanoparticles_2013) have been published. This new Special Issue “Bioactive Nanoparticles 2014” will include research papers and review articles reflecting the most recent progress and solutions to challenges in this dynamic research area.

Dr. Bing Yan 
Guest Editor

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Keywords

  • nanoparticle protein interactions
  • nanoparticle cell interaction
  • cancer-targeting nanoparticle
  • nanoparticle for drug delivery
  • nano-imaging agent
  • toxicity of nanoparticle or nanomaterials

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Published Papers (38 papers)

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952 KiB  
Article
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; https://doi.org/10.3390/ijms16059484 - 27 Apr 2015
Cited by 47 | Viewed by 7403
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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795 KiB  
Article
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; https://doi.org/10.3390/ijms16047195 - 31 Mar 2015
Cited by 26 | Viewed by 6983
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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Communication
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; https://doi.org/10.3390/ijms16023990 - 12 Feb 2015
Cited by 31 | Viewed by 6593
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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2561 KiB  
Article
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; https://doi.org/10.3390/ijms16023188 - 02 Feb 2015
Cited by 22 | Viewed by 5687
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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Article
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; https://doi.org/10.3390/ijms16012034 - 16 Jan 2015
Cited by 17 | Viewed by 8678
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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1855 KiB  
Article
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; https://doi.org/10.3390/ijms16011131 - 05 Jan 2015
Cited by 55 | Viewed by 10858
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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2747 KiB  
Article
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; https://doi.org/10.3390/ijms16010907 - 31 Dec 2014
Cited by 28 | Viewed by 11654
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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2290 KiB  
Article
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; https://doi.org/10.3390/ijms16010660 - 30 Dec 2014
Cited by 11 | Viewed by 7004
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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Article
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; https://doi.org/10.3390/ijms16010148 - 24 Dec 2014
Cited by 21 | Viewed by 6369
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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4227 KiB  
Article
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; https://doi.org/10.3390/ijms151223909 - 22 Dec 2014
Cited by 60 | Viewed by 9636
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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3483 KiB  
Article
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; https://doi.org/10.3390/ijms151222960 - 11 Dec 2014
Cited by 32 | Viewed by 8844
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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3201 KiB  
Article
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; https://doi.org/10.3390/ijms151222563 - 05 Dec 2014
Cited by 23 | Viewed by 6838
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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1857 KiB  
Article
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; https://doi.org/10.3390/ijms151121538 - 24 Nov 2014
Cited by 16 | Viewed by 5916
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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Article
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; https://doi.org/10.3390/ijms151121253 - 17 Nov 2014
Cited by 146 | Viewed by 13353
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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Article
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; https://doi.org/10.3390/ijms151120469 - 07 Nov 2014
Cited by 28 | Viewed by 7783
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, [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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Article
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; https://doi.org/10.3390/ijms151019239 - 23 Oct 2014
Cited by 28 | Viewed by 9078
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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Article
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; https://doi.org/10.3390/ijms151017565 - 29 Sep 2014
Cited by 43 | Viewed by 7666
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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Article
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; https://doi.org/10.3390/ijms150916936 - 23 Sep 2014
Cited by 19 | Viewed by 7067
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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Article
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; https://doi.org/10.3390/ijms150916057 - 11 Sep 2014
Cited by 52 | Viewed by 8080
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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Article
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; https://doi.org/10.3390/ijms150915981 - 10 Sep 2014
Cited by 21 | Viewed by 7676
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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Article
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; https://doi.org/10.3390/ijms150813649 - 07 Aug 2014
Cited by 1 | Viewed by 6036
Abstract
We have successfully synthesized SiO2@(Y0.5Gd0.45Eu0.05)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 [...] Read more.
We have successfully synthesized SiO2@(Y0.5Gd0.45Eu0.05)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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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Article
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; https://doi.org/10.3390/ijms150712379 - 14 Jul 2014
Cited by 58 | Viewed by 9056
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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Article
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; https://doi.org/10.3390/ijms150711742 - 02 Jul 2014
Cited by 30 | Viewed by 8098
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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Article
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; https://doi.org/10.3390/ijms15057293 - 28 Apr 2014
Cited by 14 | Viewed by 10299
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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Article
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; https://doi.org/10.3390/ijms15046857 - 22 Apr 2014
Cited by 73 | Viewed by 11105
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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Article
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; https://doi.org/10.3390/ijms15033373 - 25 Feb 2014
Cited by 67 | Viewed by 9922
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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Article
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; https://doi.org/10.3390/ijms15022761 - 18 Feb 2014
Cited by 35 | Viewed by 7471 | Correction
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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Article
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; https://doi.org/10.3390/ijms15022695 - 17 Feb 2014
Cited by 9 | Viewed by 7639
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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Article
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; https://doi.org/10.3390/ijms141224320 - 13 Dec 2013
Cited by 75 | Viewed by 8810
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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Article
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; https://doi.org/10.3390/ijms141224305 - 13 Dec 2013
Cited by 17 | Viewed by 8773
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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328 KiB  
Article
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; https://doi.org/10.3390/ijms141224074 - 11 Dec 2013
Cited by 65 | Viewed by 7680
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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Review

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1425 KiB  
Review
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; https://doi.org/10.3390/ijms16034880 - 04 Mar 2015
Cited by 239 | Viewed by 17112
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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1916 KiB  
Review
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; https://doi.org/10.3390/ijms16011772 - 13 Jan 2015
Cited by 68 | Viewed by 11338
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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Graphical abstract

1060 KiB  
Review
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; https://doi.org/10.3390/ijms16010230 - 24 Dec 2014
Cited by 13 | Viewed by 8421
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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1763 KiB  
Review
Mechanistic Understanding of Toxicity from Nanocatalysts
by Cuijuan Jiang, Jianbo Jia and Shumei Zhai
Int. J. Mol. Sci. 2014, 15(8), 13967-13992; https://doi.org/10.3390/ijms150813967 - 12 Aug 2014
Cited by 20 | Viewed by 8056
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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1358 KiB  
Review
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; https://doi.org/10.3390/ijms150813720 - 08 Aug 2014
Cited by 87 | Viewed by 10344
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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711 KiB  
Review
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; https://doi.org/10.3390/ijms15057409 - 29 Apr 2014
Cited by 92 | Viewed by 10733
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 [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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986 KiB  
Review
Nanotoxicity Overview: Nano-Threat to Susceptible Populations
by Yang Li, Yi Zhang and Bing Yan
Int. J. Mol. Sci. 2014, 15(3), 3671-3697; https://doi.org/10.3390/ijms15033671 - 28 Feb 2014
Cited by 85 | Viewed by 10750
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, [...] Read more.
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
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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