In vitro and in vivo effects of graphene oxide and reduced graphene oxide on glioblastoma

Graphene and its related counterparts are considered the future of advanced nanomaterials owing to their exemplary properties. However, information about their toxicity and biocompatibility is limited. The objective of this study is to evaluate the toxicity of graphene oxide (GO) and reduced graphene oxide (rGO) platelets, using U87 and U118 glioma cell lines for an in vitro model and U87 tumors cultured on chicken embryo chorioallantoic membrane for an in vivo model. The in vitro investigation consisted of structural analysis of GO and rGO platelets using transmission electron microscopy, evaluation of cell morphology and ultrastructure, assessment of cell viability by XTT assay, and investigation of cell proliferation by BrdU assay. Toxicity in U87 glioma tumors was evaluated by calculation of weight and volume of tumors and analyses of ultrastructure, histology, and protein expression. The in vitro results indicate that GO and rGO enter glioma cells and have different cytotoxicity. Both types of platelets reduced cell viability and proliferation with increasing doses, but rGO was more toxic than GO. The mass and volume of tumors were reduced in vivo after injection of GO and rGO. Moreover, the level of apoptotic markers increased in rGO-treated tumors. We show that rGO induces cell death mostly through apoptosis, indicating the potential applicability of graphene in cancer therapy.