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      Toxicity of Nanoparticles and an Overview of Current Experimental Models

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          Abstract

          Nanotechnology is a rapidly growing field having potential applications in many areas. Nanoparticles (NPs) have been studied for cell toxicity, immunotoxicity, and genotoxicity. Tetrazolium-based assays such as MTT, MTS, and WST-1 are used to determine cell viability. Cell inflammatory response induced by NPs is checked by measuring inflammatory biomarkers, such as IL-8, IL-6, and tumor necrosis factor, using ELISA. Lactate dehydrogenase (LDH) assay is used for cell membrane integrity. Different types of cell cultures, including cancer cell lines have been employed as in vitro toxicity models. It has been generally agreed that NPs interfere with either assay materials or with detection systems. So far, toxicity data generated by employing such models are conflicting and inconsistent. Therefore, on the basis of available experimental models, it may be difficult to judge and list some of the more valuable NPs as more toxic to biological systems and vice versa. Considering the potential applications of NPs in many fields and the growing apprehensions of FDA about the toxic potential of nanoproducts, it is the need of the hour to look for new internationally agreed free of bias toxicological models by focusing more on in vivo studies.

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          Most cited references97

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          Nanosilver: a nanoproduct in medical application.

          Nanotechnology is a most promising field for generating new applications in medicine. However, only few nanoproducts are currently in use for medical purposes. A most prominent nanoproduct is nanosilver. Nanosilver particles are generally smaller than 100nm and contain 20-15,000 silver atoms. At nanoscale, silver exhibits remarkably unusual physical, chemical and biological properties. Due to its strong antibacterial activity, nanosilver coatings are used on various textiles but as well as coatings on certain implants. Further, nanosilver is used for treatment of wounds and burns or as a contraceptive and marketed as a water disinfectant and room spray. Thus, use of nanosilver is becoming more and more widespread in medicine and related applications and due to increasing exposure toxicological and environmental issues need to be raised. In sharp contrast to the attention paid to new applications of nanosilver, few studies provide only scant insights into the interaction of nanosilver particle with the human body after entering via different portals. Biodistribution, organ accumulation, degradation, possible adverse effects and toxicity are only slowly recognized and this review is focusing on major questions associated with the increased medical use of nanosilver and related nanomaterials.
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            In vitro toxicity of nanoparticles in BRL 3A rat liver cells.

            This study was undertaken to address the current deficient knowledge of cellular response to nanosized particle exposure. The study evaluated the acute toxic effects of metal/metal oxide nanoparticles proposed for future use in industrial production methods using the in vitro rat liver derived cell line (BRL 3A). Different sizes of nanoparticles such as silver (Ag; 15, 100 nm), molybdenum (MoO(3); 30, 150 nm), aluminum (Al; 30, 103 nm), iron oxide (Fe(3)O(4); 30, 47 nm), and titanium dioxide (TiO(2); 40 nm) were evaluated for their potential toxicity. We also assessed the toxicity of relatively larger particles of cadmium oxide (CdO; 1 microm), manganese oxide (MnO(2); 1-2 microm), and tungsten (W; 27 microm), to compare the cellular toxic responses with respect to the different sizes of nanoparticles with different core chemical compositions. For toxicity evaluations, cellular morphology, mitochondrial function (MTT assay), membrane leakage of lactate dehydrogenase (LDH assay), reduced glutathione (GSH) levels, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were assessed under control and exposed conditions (24h of exposure). Results showed that mitochondrial function decreased significantly in cells exposed to Ag nanoparticles at 5-50 microg/ml. However, Fe(3)O(4), Al, MoO(3) and TiO(2) had no measurable effect at lower doses (10-50 microg/ml), while there was a significant effect at higher levels (100-250 microg/ml). LDH leakage significantly increased in cells exposed to Ag nanoparticles (10-50 microg/ml), while the other nanoparticles tested displayed LDH leakage only at higher doses (100-250 microg/ml). In summary the Ag was highly toxic whereas, MoO(3) moderately toxic and Fe(3)O(4), Al, MnO(2) and W displayed less or no toxicity at the doses tested. The microscopic studies demonstrated that nanoparticle-exposed cells at higher doses became abnormal in size, displaying cellular shrinkage, and an acquisition of an irregular shape. Due to toxicity of silver, further study conducted with reference to its oxidative stress. The results exhibited significant depletion of GSH level, reduced mitochondrial membrane potential and increase in ROS levels, which suggested that cytotoxicity of Ag (15, 100 nm) in liver cells is likely to be mediated through oxidative stress.
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              Gold nanoparticles as novel agents for cancer therapy.

              Gold nanoparticles are emerging as promising agents for cancer therapy and are being investigated as drug carriers, photothermal agents, contrast agents and radiosensitisers. This review introduces the field of nanotechnology with a focus on recent gold nanoparticle research which has led to early-phase clinical trials. In particular, the pre-clinical evidence for gold nanoparticles as sensitisers with ionising radiation in vitro and in vivo at kilovoltage and megavoltage energies is discussed.
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                Author and article information

                Journal
                Iran Biomed J
                Iran. Biomed. J
                IBJ
                Iranian Biomedical Journal
                Pasteur Institute of Iran (Tehran, Iran )
                1028-852X
                2008-823X
                January 2016
                : 20
                : 1
                : 1-11
                Affiliations
                [1 ]Dept. of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, International Campus, Tehran University of Medical Sciences, Tehran, Iran;
                [2 ]Endocrinology and Metabolism Research Center, Institute of Clinical Endocrine Sciences, Tehran University of Medical Sciences, Tehran, Iran;
                [3 ]Toxicology and Poisoning Research Center, Tehran University of Medical Sciences, Tehran, Iran
                Author notes
                [* ]Corresponding Author: Mohammad Abdollahi , Dept. of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, International Campus, Tehran University of Medical Sciences, Tehran, Iran; Tel/Fax: (+98-21) 66959104; E-mail: Mohammad.Abdollahi@UToronto.Ca, Mohammad@TUMS.ac.Ir
                Article
                10.7508/ibj.2016.01.001
                4689276
                26286636
                98465a28-eaab-4117-bc11-671f260943e3

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 6 June 2015
                : 25 July 2015
                : 1 August 2015
                Categories
                Review Article

                cytotoxicity,in vitro,metal nanoparticles,toxicology,review
                cytotoxicity, in vitro, metal nanoparticles, toxicology, review

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