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Investigating oxidation state-induced toxicity of PEGylated graphene oxide in ocular tissue using gene expression profiles

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posted on 2018-06-09, 10:19 authored by Wei Wu, Liang Yan, Siyu Chen, Qiyou Li, Zhanjun Gu, Haiwei Xu, Zheng Qin Yin

Graphene and its derivatives are widely used for a variety of industrial, biomedical, and environmental applications. However, the potential harm caused by exposure of the eyes to graphene-based nanomaterials is scarce. Given the potential for these materials to be used in multiple applications, there is a pressing need to evaluate their ocular toxicity, and understand the relationships between their physico-chemical properties and the resulting toxicity. In this study, the toxicity of PEGylated graphene oxide (PEG-GO) with differing oxidation levels and/or surface charges (positive, negative and neutral charge) was evaluated using two in-vitro models of the eye: primary human corneal epithelial cells and human retinal capillary endothelial cells. The results showed that oxidation level, but not surface charge, had a pivotal effect on the toxicity of graphene-based nanomaterials. Typically, PEG-GO sample with a higher oxidation level caused more serious cytotoxicity than those with a lower oxidation level. Furthermore, by analysis of global gene expression profiles, we found that the foremost cellular response to PEG-GO sample with a high oxidation level was the oxidative stress response. Next, via exploring the underlying molecular mechanism of oxidative stress-induced cytotoxicity, we showed that PEG-GO sample with a high degree of oxidation induced reactive oxygen species (ROS) via NDUFB9-mediated biological pathway. This work has significant implications for design of safe graphene-based nanomaterials for biomedical applications.

Funding

This work was supported by the National Basic Research Program of China [973 Program, 2013CB967002], National Natural Science Foundation of China [81700880],National Key Research and Development Program of China [2018YFA0107302] and Foundation of Southwest Hospital [SWH2016JSYB-01 and SWH2016LHYS-03].

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