Mitochondrial-Targeted Polyethylenimine Functionalized Graphene Oxide Nanocarrier and its Anti-Tumor Effect on Human Lung Carcinoma Cells

Abstract

Graphene oxide nanosheet (NGO) was covalently functionalized with positively charged, branched polyethylenimine (bPEI) via an amide bond, coated with serum proteins by electrostatic interaction. Operating as a newly fashioned, multifunctional nanocarrier, the processed NGO showed promise for use in combined gene therapy, chemotherapy, photothermal therapy, bioimaging and as a biosensor of cancer cells. Our current research is focused on the systematic studies of mechanisms of cancer cellular uptake, subcellular location, cytotoxicity and the cellular exclusion of the NGO–bPEI nanocarriers. It was observed that NGO–bPEI accumulated in the mitochondria and that long-term retention of NGO–bPEI led to a decrease in mitochondrial membrane potential while levels of reactive oxygen species increased. The mitochondrial effects associated with long-term retention of NGO–bPEI have potential as a synergistic enhancer of the cytotoxic effects of anti-cancer drugs or genes in human lung carcinoma (A549) cells. This work demonstrated the utility of NGO–bPEI-based multifunctional nanocarriers while detailing the mechanism at the cellular level and providing guidance for further research in cancer therapy.