The nanomaterial graphene oxide (GO) has attracted explosive interests in various areas. However, its performance in biological environments is still largely unknown, particularly with regard to cellular response to GO. Here we separated the GO sheets in different size and systematically investigated size effect of the GO in response to different types of cells. In terms of abilities to internalize GO, enormous discrepancies were observed in the six cell types, with only two phagocytes were found to be capable of internalizing GO. The 2 μm and 350 nm GO greatly differed in lateral dimensions, but equally contributed to the uptake amount in macrophages. Similar amounts of antibody opsonization and active Fcγ receptor-mediated phagocytosis were demonstrated the cause of this behavior. In comparison with the nanosized GO, the GO in micro-size showed divergent intracellular locations and induced much stronger inflammation responses. Present study provided insight into selective internalization, size-independent uptake, and several other biological behaviors undergone by GO. These findings might help build necessary knowledge for potential incorporation of the unique two-dimensional nanomaterial as a biomedical tool, and for avoiding potential hazards.

This paper was originally published in Biomaterials (2012) 33, 4013–4021.

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