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氧化铟纳米立方体会通过氧化应激诱导人肺上皮细胞产生细胞毒性和细胞凋亡。

Nanocubes of indium oxide induce cytotoxicity and apoptosis through oxidative stress in human lung epithelial cells.

机构信息

King Abdullah Institute for Nanotechnology, King Saud University, Riyadh, Saudi Arabia.

King Abdullah Institute for Nanotechnology, King Saud University, Riyadh, Saudi Arabia.

出版信息

Colloids Surf B Biointerfaces. 2017 Aug 1;156:157-164. doi: 10.1016/j.colsurfb.2017.05.020. Epub 2017 May 9.

DOI:10.1016/j.colsurfb.2017.05.020
PMID:28527359
Abstract

The demand for semiconductor indium oxide (InO) nanocrystals is increasing because of their diverse applications, including in biomedicine. However, there is a scarcity of studies on the biological interaction of indium oxide nanocrystals. Here, we explored the underlying mechanisms of toxicity induced by indium oxide nanocubes in human lung epithelial (A549) cells. Prepared indium oxide nanocubes were crystalline with an average size of 21nm. Biointeraction studies have shown that indium oxide nanocubes induce cell viability reduction and cell membrane damage in a dose- and time-dependent manner. Indium oxide nanocubes were also found to induce reactive oxygen species (ROS) generation, glutathione depletion and lower activity of superoxide oxide dismutase. Further, indium oxide nanocubes induced a mitochondrial membrane potential loss and altered the mRNA expression levels of apoptotic genes (p53, bax, bcl-2, CASP3 & CASP9). The activities of apoptotic enzymes (caspase-3 and -9) were also higher in indium oxide nanocube-treated cells. Finally, we observed that the cytotoxicity and apoptosis induction of indium oxide nanocubes were efficiently prevented by N-acetyl-cysteine. We believe that this is the first report suggesting that indium oxide nanocubes induce toxicity in lung cells via ROS generation and oxidative stress. This study warrants future research on the toxicity mechanisms of indium oxide nanoparticles in animal models.

摘要

由于其多样化的应用,包括在生物医学领域,对半导体氧化铟(InO)纳米晶体的需求正在增加。然而,关于氧化铟纳米晶体的生物相互作用的研究很少。在这里,我们研究了氧化铟纳米立方体在人肺上皮(A549)细胞中诱导毒性的潜在机制。制备的氧化铟纳米立方体具有结晶性,平均尺寸为 21nm。生物相互作用研究表明,氧化铟纳米立方体以剂量和时间依赖的方式诱导细胞活力降低和细胞膜损伤。还发现氧化铟纳米立方体诱导活性氧(ROS)的产生,谷胱甘肽耗竭和超氧化物歧化酶活性降低。此外,氧化铟纳米立方体诱导线粒体膜电位丧失,并改变凋亡基因(p53、bax、bcl-2、CASP3 和 CASP9)的 mRNA 表达水平。凋亡酶(caspase-3 和 -9)的活性在氧化铟纳米立方体处理的细胞中也更高。最后,我们观察到 N-乙酰半胱氨酸能有效防止氧化铟纳米立方体的细胞毒性和诱导细胞凋亡。我们相信,这是第一个表明氧化铟纳米立方体通过 ROS 生成和氧化应激诱导肺细胞毒性的报告。这项研究需要在动物模型中进一步研究氧化铟纳米粒子的毒性机制。

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