Size-dependent cytotoxicity of Fe3O4 nanoparticles induced by biphasic regulation of oxidative stress in different human hepatoma cells.
Size-dependent cytotoxicity of Fe3O4 nanoparticles induced by biphasic regulation of oxidative stress in different human hepatoma cells.
复制标题
Fe3O4 纳米颗粒在不同人肝癌细胞中氧化应激双相调节诱导的尺寸依赖性细胞毒性
DOI：
10.2147/ijn.s105575
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发表时间：
2016
影响因子：
8
通讯作者：
Liu P
中科院分区：
文献类型：
--
作者：
Xie Y;Liu D;Cai C;Chen X;Zhou Y;Wu L;Sun Y;Dai H;Kong X;Liu P
Fe 3 O 4纳米粒在疾病诊断和肿瘤治疗药物传递系统中的应用取得了很大进展，但其潜在的毒性机制尚未跟上其应用发展的步伐，阻碍了其进一步的临床应用。本文以人肝癌细胞株SK-Hep-1和Hep 3B为研究对象，探讨了不同粒径（6 nm、9 nm和14 nm）的Fe 3 O 4纳米微粒对人肝癌细胞株SK-Hep-1和Hep 3B的细胞毒作用及其机制。结果表明，纳米粒子的大小有效地影响肝癌细胞的细胞毒性：6 nm的Fe 3 O 4纳米粒子表现出可忽略的细胞毒性和9 nm的Fe 3 O 4纳米粒子通过细胞线粒体功能障碍和诱导坏死介导的细胞内活性氧的产生影响细胞毒性。同时，14 nm的Fe 3 O 4纳米颗粒通过损害质膜的完整性和促进大量的乳酸脱氢酶泄漏诱导细胞毒性。这些结果解释了不同直径的小Fe 3 O 4 NPs诱导细胞毒性的详细机制。我们期望本研究能对Fe 3 O 4纳米粒的细胞毒性机制提供不同的见解，从而使其更安全地用于临床应用。
The application of Fe3O4 nanoparticles (NPs) has made great progress in the diagnosis of disease and in the drug delivery system for cancer therapy, but the relative mechanisms of potential toxicity induced by Fe3O4 have not kept pace with its development in the application, which has hampered its further clinical application. In this article, we used two kinds of human hepatoma cell lines, SK-Hep-1 and Hep3B, to investigate the cytotoxic effects and the involved mechanisms of small Fe3O4 NPs with different diameters (6 nm, 9 nm, and 14 nm). Results showed that the size of NPs effectively influences the cytotoxicity of hepatoma cells: 6 nm Fe3O4 NPs exhibited negligible cytotoxicity and 9 nm Fe3O4 NPs affected cytotoxicity via cellular mitochondrial dysfunction and by inducing necrosis mediated through the mitochondria-dependent intracellular reactive oxygen species generation. Meanwhile, 14 nm Fe3O4 NPs induced cytotoxicity by impairing the integrity of plasma membrane and promoting massive lactate dehydrogenase leakage. These results explain the detailed mechanism of different diameters of small Fe3O4 NPs-induced cytotoxicity. We anticipate that this study will provide different insights into the cytotoxicity mechanism of Fe3O4 NPs, so as to make them safer to use in clinical application.