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      Cytotoxicity of nickel zinc ferrite nanoparticles on cancer cells of epithelial origin

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          Abstract

          In this study, in vitro cytotoxicity of nickel zinc (NiZn) ferrite nanoparticles against human colon cancer HT29, breast cancer MCF7, and liver cancer HepG2 cells was examined. The morphology, homogeneity, and elemental composition of NiZn ferrite nanoparticles were investigated by scanning electron microscopy, transmission electron microscopy, and energy dispersive X-ray spectroscopy, respectively. The exposure of cancer cells to NiZn ferrite nanoparticles (15.6–1,000 μg/mL; 72 hours) has resulted in a dose-dependent inhibition of cell growth determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The quantification of caspase-3 and -9 activities and DNA fragmentation to assess the cell death pathway of the treated cells showed that both were stimulated when exposed to NiZn ferrite nanoparticles. Light microscopy examination of the cells exposed to NiZn ferrite nanoparticles demonstrated significant changes in cellular morphology. The HepG2 cells were most prone to apoptosis among the three cells lines examined, as the result of treatment with NiZn nanoparticles. In conclusion, NiZn ferrite nanoparticles are suggested to have potential cytotoxicity against cancer cells.

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          Most cited references 36

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          The sensitivity and specificity of the MTS tetrazolium assay for detecting the in vitro cytotoxicity of 20 chemicals using human cell lines.

          A number of studies reported that the MTS in vitro cytotoxicity assay is a convenient method for assessing cell viability. The main features found with this assay are its ease of use, accuracy and rapid indication of toxicity. It might well be a useful tool in human health risk assessment if it can be shown that this assay also has an acceptable sensitivity and specificity. This is of interest particularly when exposure to unknown chemical substances requires the rapid detection and evaluation of toxic effects. In this study, the cytotoxicity of 20 chemicals selected from the MEIC priority list was determined with the MTS assay. Since it could be shown that interactions between detection reagents and test chemicals might influence the results of this assay, preliminary experiments were carried out such that artifactual results due to test chemical interference could be excluded from this study. IC50 (50% inhibitory concentration) were established for each test chemical in two human cell lines (F1-73 and HeLa) and later compared with published toxicity data of the same chemicals established with in vitro and in vivo toxicological test systems. Direct comparisons of the data showed a generally lower sensitivity of the MTS assay, which is influenced by biological test organisms, cell type and exposure time. In terms of the specificity of the MTS assay, the results showed a good correlation between data obtained with the MTS assay and published data. The lowest correlation was found when the MTS assay was compared with in vivo studies, however, this finding corresponds well with other published in vitro-in vivo correlations. The highest correlation was found when the MTS assay was compared with test systems using human cell lines or exposure times of 3-24 h. Since the sensitivity of the MTS assay might be increased using different cell types or by extended incubation, this assay is found to provide ideal features of a good measurement system that might also be used for on site toxicological assessments.
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            Multifunctional doxorubicin loaded superparamagnetic iron oxide nanoparticles for chemotherapy and magnetic resonance imaging in liver cancer.

            To develop a drug delivery system with enhanced efficacy and minimized adverse effects, we synthesized a novel polymeric nanoparticles, (YCC-DOX) composed of poly (ethylene oxide)-trimellitic anhydride chloride-folate (PEO-TMA-FA), doxorubicin (DOX) and superparamagnetic iron oxide (Fe(3)O(4)) and folate. The efficacy of the nanoparticles was evaluated in rats and rabbits with liver cancer, in comparison with free-DOX (FD) and a commercial liposome drug, DOXIL. YCC-DOX showed the anticancer efficacy and specifically targeted folate receptor (FR)-expressing tumors, thereby increasing the bioavailability and efficacy of DOX. The relative tumor volume of the YCC-DOX group was decreased two- and four-fold compared with the FD and DOXIL groups in the rat and rabbit models, respectively. Furthermore, YCC-DOX showed higher MRI sensitivity comparable to a conventional MRI contrast agent (Resovist), even in its lower iron content. In the immunohistochemical analysis, YCC-DOX group showed the lower expression of CD34 and Ki-67, markers of angiogenesis and cell proliferation, respectively, while apoptotic cells were significantly rich in the YCC-DOX group in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. These results indicate that YCC-DOX is a promising candidate for treating liver cancer and monitoring the progress of the cancer using MRI. (c) 2010. Published by Elsevier Ltd. All rights reserved.
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              Oxidative stress mediated apoptosis induced by nickel ferrite nanoparticles in cultured A549 cells.

              Due to the interesting magnetic and electrical properties with good chemical and thermal stabilities, nickel ferrite nanoparticles are being utilized in many applications including magnetic resonance imaging, drug delivery and hyperthermia. Recent studies have shown that nickel ferrite nanoparticles produce cytotoxicity in mammalian cells. However, there is very limited information concerning the toxicity of nickel ferrite nanoparticles at the cellular and molecular level. The aim of this study was to investigate the cytotoxicity, oxidative stress and apoptosis induction by well-characterized nickel ferrite nanoparticles (size 26 nm) in human lung epithelial (A549) cells. Nickel ferrite nanoparticles induced dose-dependent cytotoxicity in A549 cells demonstrated by MTT, NRU and LDH assays. Nickel ferrite nanoparticles were also found to induce oxidative stress evidenced by generation of reactive oxygen species (ROS) and depletion of antioxidant glutathione (GSH). Further, co-treatment with the antioxidant L-ascorbic acid mitigated the ROS generation and GSH depletion due to nickel ferrite nanoparticles suggesting the potential mechanism of oxidative stress. Quantitative real-time PCR analysis demonstrated that following the exposure of A549 cells to nickel ferrite nanoparticles, the level of mRNA expressions of cell cycle checkpoint protein p53 and apoptotic proteins (bax, caspase-3 and caspase-9) were significantly up-regulated, whereas the expression of anti-apoptotic proteins (survivin and bcl-2) were down-regulated. Moreover, activities of caspase-3 and caspase-9 enzymes were also significantly higher in nickel ferrite nanoparticles exposed cells. To the best of our knowledge this is the first report showing that nickel ferrite nanoparticles induced apoptosis in A549 cells through ROS generation and oxidative stress via p53, survivin, bax/bcl-2 and caspase pathways. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
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                Author and article information

                Journal
                Int J Nanomedicine
                Int J Nanomedicine
                International Journal of Nanomedicine
                Dove Medical Press
                1176-9114
                1178-2013
                2013
                2013
                15 July 2013
                : 8
                : 2497-2508
                Affiliations
                [1 ]Institute of Bioscience, Universiti Putra Malaysia, Selangor, Malaysia
                [2 ]Faculty of Veterinary Medicine, Universiti Putra Malaysia, Selangor, Malaysia
                [3 ]Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, Selangor, Malaysia
                [4 ]Faculty of Food Science and Technology, Universiti Putra Malaysia, Selangor, Malaysia
                [5 ]School of Applied Physics, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Selangor, Malaysia
                [6 ]College of Pharmacy, Qassim University, Buraidah, Saudi Arabia
                [7 ]Faculty of Pharmacy, Zagazig University, Ash Sharqiyah, Egypt
                Author notes
                Correspondence: Rasedee Abdullah, Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia, Tel +603 8946 3455, Fax +603 8946 1971, Email rasedee@ 123456vet.upm.edu.my
                Article
                ijn-8-2497
                10.2147/IJN.S42367
                3716602
                23885175
                © 2013 Al-Qubaisi et al, publisher and licensee Dove Medical Press Ltd

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

                Categories
                Original Research

                Molecular medicine

                nizn ferrite nanoparticles, cancer cells lines, anticancer, apoptosis

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