Cytotoxicity and Genotoxicity of Silver Nanoparticles in Human Cells
Cytotoxicity and Genotoxicity of Silver Nanoparticles in Human Cells
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DOI：
10.1021/nn800596w
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发表时间：
2009-02-01
期刊：
影响因子：
17.1
通讯作者：
Valiyaveettil, Suresh
中科院分区：
文献类型：
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作者：
AshaRani, P. V.;Mun, Grace Low Kah;Valiyaveettil, Suresh
银纳米颗粒（Ag-np）由于其抗微生物活性而越来越多地用于伤口敷料、导管和各种家用产品。使用正常人肺成纤维细胞（IMR-90）和人胶质母细胞瘤细胞（U251）研究淀粉涂层银纳米颗粒的毒性。使用细胞形态学、细胞活力、代谢活性和氧化应激的变化评价毒性。Ag-np降低细胞ATP含量，引起线粒体损伤，并以剂量依赖性方式增加活性氧（ROS）的产生。通过单细胞凝胶电泳（SCGE）和胞质分裂阻滞微核试验（CBMN）测量的DNA损伤也具有剂量依赖性，并且在癌细胞中更为突出。纳米颗粒处理导致细胞周期停滞在G（2）/M期，可能是由于修复受损的DNA。Annexin-V碘化丙啶（PI）染色显示无大量凋亡或坏死。透射电子显微镜分析表明Ag-np存在于线粒体和细胞核内，暗示它们直接参与线粒体毒性和DNA损伤。提出了一种可能的毒性机制，其涉及Ag-np破坏线粒体呼吸链，导致ROS的产生和ATP合成的中断，这反过来又导致DNA损伤。预期DNA损伤通过沉积而增强，随后Ag-np与DNA的相互作用导致细胞周期停滞在G（2）/M期。U251细胞对Ag-np的高敏感性及其G2/M期阻滞可为Ag-np在肿瘤治疗中的应用提供新的思路。
Silver nanoparticles (Ag-np) are being used increasingly in wound dressings, catheters, and various household products due to their antimicrobial activity. The toxicity of starch-coated silver nanoparticles was studied using normal human lung fibroblast cells (IMR-90) and human glioblastoma cells (U251). The toxicity was evaluated using changes in cell morphology, cell viability, metabolic activity, and oxidative stress. Ag-np reduced ATP content of the cell caused damage to mitochondria and increased production of reactive oxygen species (ROS) in a dose-dependent manner. DNA damage, as measured by single cell gel electrophoresis (SCGE) and cytokinesis blocked micronucleus assay (CBMN), was also dose-dependent and more prominent in the cancer cells. The nanoparticle treatment caused cell cycle arrest in G(2)/M phase possibly due to repair of damaged DNA. Annexin-V propidium iodide (PI) staining showed no massive apoptosis or necrosis. The transmission electron microscopic ITEM) analysis indicated the presence of Ag-np inside the mitochondria and nucleus, implicating their direct involvement in the mitochondrial toxicity and DNA damage. A possible mechanism of toxicity is proposed which involves disruption of the mitochondrial respiratory chain by Ag-np leading to production of ROS and interruption of ATP synthesis, which in turn cause DNA damage. It is anticipated that DNA damage is augmented by deposition, followed by interactions of Ag-np to the DNA leading to cell cycle arrest in the G(2)/M phase. The higher sensitivity of U251 cells and their arrest in G2/M phase could be explored further for evaluating the potential use of Ag-np in cancer therapy.