PEGylated graphene oxide elicits strong immunological responses despite surface passivation

Nana Luo, Jeffrey K. Weber, Shuang Wang, Binquan Luan, Hua Yue, Xiaobo Xi, Jing Du, Zaixing Yang, Wei Wei (), Ruhong Zhou () and Guanghui Ma ()
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Nana Luo: State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences
Jeffrey K. Weber: Computational Biology Center, IBM Thomas J. Watson Research Center
Shuang Wang: State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences
Binquan Luan: Computational Biology Center, IBM Thomas J. Watson Research Center
Hua Yue: State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences
Xiaobo Xi: State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences
Jing Du: Institute of Biomechanics and Medical Engineering, Tsinghua University
Zaixing Yang: Institute of Quantitative Biology and Medicine, SRMP and RAD-X, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University
Wei Wei: State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences
Ruhong Zhou: Computational Biology Center, IBM Thomas J. Watson Research Center
Guanghui Ma: State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: Abstract Engineered nanomaterials promise to transform medicine at the bio–nano interface. However, it is important to elucidate how synthetic nanomaterials interact with critical biological systems before such products can be safely utilized in humans. Past evidence suggests that polyethylene glycol-functionalized (PEGylated) nanomaterials are largely biocompatible and elicit less dramatic immune responses than their pristine counterparts. We here report results that contradict these findings. We find that PEGylated graphene oxide nanosheets (nGO-PEGs) stimulate potent cytokine responses in peritoneal macrophages, despite not being internalized. Atomistic molecular dynamics simulations support a mechanism by which nGO-PEGs preferentially adsorb onto and/or partially insert into cell membranes, thereby amplifying interactions with stimulatory surface receptors. Further experiments demonstrate that nGO-PEG indeed provokes cytokine secretion by enhancing integrin β8-related signalling pathways. The present results inform that surface passivation does not always prevent immunological reactions to 2D nanomaterials but also suggest applications for PEGylated nanomaterials wherein immune stimulation is desired.

Date: 2017
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DOI: 10.1038/ncomms14537

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