Immune response is required for the control of in vivo translocation and chronic toxicity of graphene oxide
Immune response is required for the control of in vivo translocation and chronic toxicity of graphene oxide
复制标题
免疫反应是控制氧化石墨烯体内易位和慢性毒性所必需的
DOI：
10.1039/c4nr00699b
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发表时间：
2014-06-07
期刊：
影响因子：
6.7
通讯作者：
Wang, Dayong
中科院分区：
文献类型：
--
作者：
Wu, Qiuli;Zhao, Yunli;Wang, Dayong
氧化石墨烯（GO）作为一种纳米材料在医疗应用中显示出巨大的前景;然而，其长期不良反应的机制仍不清楚。在这里，我们表明，慢性GO暴露不仅造成损害的主要和次要目标器官的功能，但也诱导严重积累的致病微生物食物（OP 50）在肠道的秀丽隐杆线虫，非哺乳动物的替代毒性测定系统。GO在肠道内的蓄积可与OP 50大量共定位，并导致动物免疫应答下降。相反，用UV处理的OP 50饲喂抑制了GO毒性和在肠道中的积累，并维持了动物相对正常的免疫应答。结论：GO对AVL和DVB神经元的发育和功能有一定的影响，可能是导致OP 50在肠道内大量蓄积的原因之一。通过PEG表面修饰降低慢性GO毒性主要是由于抑制了OP 50在肠道中的积累和维持了正常的免疫应答。我们的研究结果强调了先天免疫在调节体内慢性GO毒性中的关键作用，这将有助于我们了解纳米材料与生物系统在动物长期发育过程中的相互作用。
Graphene oxide (GO) shows great promise as a nanomaterial for medical applications; however, the mechanism for its long-term adverse effects is still largely unclear. Here, we show that chronic GO exposure not only caused damage on the function of both primary and secondary targeted organs but also induced severe accumulation of pathogenic microbial food (OP50) in the intestine of Caenorhabditis elegans, a non-mammalian alternative toxicity assay system. GO accumulated in the intestine could be largely co-localized with OP50 and induced decreased immune response of animals. In contrast, feeding with UV-treated OP50 suppressed GO toxicity and accumulation in the intestine and maintained the relatively normal immune response of animals. The severe accumulation of OP50 in the intestine might be partially due to the damage by GO on the development and function of AVL and DVB neurons controlling defecation behavior. Reduction of chronic GO toxicity by PEG surface modification largely resulted from the inhibition of OP50 accumulation in the intestine and the maintenance of normal immune response. Our results highlight the key role of innate immunity in regulating in vivo chronic GO toxicity, which will be helpful for our understanding of the interactions between nanomaterials and biological systems during the long-term development of animals.