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

Abstract

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.

Keywords:

• Cytotoxicity
• graphene oxide
• physico-chemical properties
• gene expression profiles
• oxidative stress

Acknowledgments

We are grateful to Q. Wu for kindly help.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

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].