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小金纳米颗粒暴露下的小气道上皮细胞的毒理学特征。

Toxicological profile of small airway epithelial cells exposed to gold nanoparticles.

机构信息

Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, S117597 Singapore.

出版信息

Exp Biol Med (Maywood). 2013 Dec;238(12):1355-61. doi: 10.1177/1535370213505964. Epub 2013 Oct 24.

Abstract

Gold nanoparticles (AuNPs) have diverse applications in the biomedical industry such as in diagnosis, labeling, delivering and sensing. Despite their prevalent medical use, nanotoxicity induced by AuNPs is still largely unknown. We have previously shown that AuNPs could exert cytotoxic effects on lung fibroblasts. In this study, we investigated the in vitro toxicological effects of AuNPs in small airway epithelial cells (SAECs) which are the first cells of contact for inhaled NPs and compared expression of metallothionein (MT), a reactive oxygen species scavenger, in SAECs and lung fibroblasts in vitro. Transmission electron microscopy (TEM) and energy-dispersive X-ray (EDX) spectroscopy study revealed cellular uptake of aggregates of AuNPs into the cytoplasm at the ultrastructural level. A significant increase in lipid peroxide as well as substantial DNA damage and cytotoxicity was observed in AuNP-treated cells. For MT expression, AuNPs induced down-regulation of the MT-1X isoform in SAECs, but up-regulation of the MT-1X and MT-2 A isoforms in MRC5 lung fibroblasts. The present study suggests that AuNPs could induce oxidative stress-related cytotoxicity and genotoxicity in SAECs.

摘要

金纳米粒子(AuNPs)在生物医药行业中有多种应用,如诊断、标记、输送和传感。尽管它们在医学上得到了广泛的应用,但 AuNPs 诱导的纳米毒性在很大程度上仍然未知。我们之前已经表明,AuNPs 可能对肺成纤维细胞产生细胞毒性作用。在这项研究中,我们研究了 AuNPs 在小气道上皮细胞(SAECs)中的体外毒理学效应,SAECs 是吸入 NPs 的第一接触细胞,并比较了 MT(一种活性氧清除剂)在 SAECs 和肺成纤维细胞中的表达。透射电子显微镜(TEM)和能谱(EDX)研究揭示了 AuNPs 聚集体在超微结构水平上被细胞摄取到细胞质中。在 AuNP 处理的细胞中观察到脂质过氧化物的显著增加以及大量的 DNA 损伤和细胞毒性。对于 MT 表达,AuNPs 诱导 SAECs 中 MT-1X 同工型的下调,但诱导 MRC5 肺成纤维细胞中 MT-1X 和 MT-2A 同工型的上调。本研究表明,AuNPs 可能在 SAECs 中诱导氧化应激相关的细胞毒性和遗传毒性。

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