Biocompatibility of graphene oxide intravenously administrated in mice—effects of dose, size and exposure protocols

Abstract

Graphene oxide (GO) shows great promise in in vivo drug delivery and therapy applications. However, several reports have reported an in vivo toxicity of GO. In this study, we found that the toxicity of GO intravenously injected into mice could be tuned by dose, size and exposure protocols of GO. The exposure to a single dose of 2.1 mg kg⁻¹ (single-high-dose exposure) small size GO or large size GO caused macrophage nodule formation in the lungs of the mice, and the exposure to seven repeated doses of 0.3 mg kg⁻¹ (multiple-low-dose exposure) large size GO also induced small macrophage nodule formation, serious lymphocyte infiltration around the bronchioles in the lungs of the mice, and even death of the mice. Nephritic inflammatory reactions were also observed after the multiple-low-dose exposure to large size GO. However, no obvious lung toxicity but hepatic inflammatory infiltration was observed after the exposure to multiple-low-dose small size GO. GO accumulation in the macrophage nodules was verified by Raman mapping. These findings will benefit the applications of GO in the future, especially in biomedical fields.