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标题：One low-dose exposure of gold nanoparticles induces long-term changes in human cells
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作者：Priscila Falagan-Lotsch ; Elissa M. Grzincic ; Catherine J. Murphy 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：47
页码：13318-13323
DOI：10.1073/pnas.1616400113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceGold nanoparticles are promising candidates for optical sensing, bioimaging, delivery, and therapeutic applications due to their size- and shape-dependent physical properties and inherent biocompatibility compared with other metallic nanoparticles. Many studies have found that these particles are generally nontoxic at low doses for most, but not all, initial surface treatments. In this study, a long-term (20 wk) exposure of a set of gold nanoparticles to a human cell line was performed in two ways: an acute burst of nanoparticle exposure compared with a continuous, chronic exposure at the same concentration. Overall, it was found that an acute burst of exposure is more harmful to cells, and that cells can adapt to long-term nanoparticle exposure. We report the in vitro long-term (20 wk) changes in cells exposed to well-characterized gold nanoparticles (Au NPs) with varying shapes and surface coatings under both chronic (exposure to Au NPs continuously over 20 wk) and nonchronic (initial acute cell exposure to Au NPs, followed by 20 wk in NP-free cell media) conditions. Both chronic and nonchronic Au NPs exposures at low dose induce modifications at the gene level after long periods. In attempt to overcome from the injuries caused by nanoparticle exposure, genes related to oxidative stress, cell cycle regulation, and inflammation are among those presenting differential expression levels. Surprisingly, the nonchronic exposure induced more gene expression changes than its chronic counterpart and the stress effects caused by this type of exposure were sustained even after 20 wk without any additional NP exposure. NP surface chemistry played an important role in the alteration of gene regulation. Overall, our data suggest that (i) cells can adaptively respond to chronic, low-level NP insults; (ii) the cell stress response is not reversible over time upon removal of NPs upon acute, nonchronic exposure; and (iii) polyethylene glycol is not as benign a surface chemistry as is generally supposed.
关键词：gold nanoparticles ; acute exposure ; chronic exposure ; surface chemistry ; gene expression