Selective toxicity of functionalised graphene oxide to patients-derived glioblastoma stem cells and minimal toxicity to non-cancerous brain tissue cells

Abstract

Glioblastoma (GBMs) is an aggressive type of brain tumour, driven by immature neural stem cell-like cells that promote tumour growth and underlie resistance to conventional therapy. The GBM stem cells (GSCs) can exist in quiescent or dormant states and infiltrate widely into surrounding brain tissues, currently incurable with only around one-year median survival. Innovative therapeutic strategies for GBMs are urgently needed. Here we explore functionalized graphene oxide (GO) to assess their value as delivery vehicles for GBM therapeutics. Interactions and cellular responses were assessed in vitro using both classic cell lines and patient derived GSCs. Association between the functionalised GO and established GBM cell lines (serum grown ‘non-stem’ cells) was strong and resulted in decreased cell viability, increased cell oxidative stress, and changes in lipids composition in a concentration-dependent manner. Responses were more moderate in GSCs and were only observed at highest functionalised GO concentrations. However, no significant toxicity was detected in brain astrocytes and endothelial cells. These results indicate selective toxicity to highly proliferative GBM cell lines and patient GSCs, with minimal toxicity to normal neural cells and brain tissue. We conclude that a novel class of GBM-targeting graphene-based nanocarriers could be useful delivery vehicles for GBM therapeutics.