Cytochrome c light-up graphene oxide nanosensor for the targeted self-monitoring of mitochondria-mediated tumor cell death

Abstract

Targeting mitochondria-mediated apoptosis has emerged as a promising strategy for tumor therapy. However, technologies used to treat tumors that enable the direct visualization of mitochondria-mediated apoptosis in living cells have not been developed to date. Cytochrome c (Cyt c) translocation from mitochondria is a central mediating event in cell apoptosis. In this study, we developed a multifunctional nanosensor that can monitor the real-time translocation of Cyt c from mitochondria in living cells to evaluate the antitumor effect of dihydroartemisinin (DHA). A fluorophore-tagged DNA aptamer is loaded on a graphene oxide (GO)-based nanovehicle, and the cytosolic release of Cyt c causes the dissociation of the aptamer from the GO nanovehicle and triggers the emission of a red fluorescence signal. Furthermore, DHA linked with a coumarin derivative is loaded on GO as a mitochondria-targeting ligand to improve its antitumor activity. This DHA prodrug also emits a green fluorescence signal when delivered to mitochondria. This nanosensor provides a convenient mechanism to monitor mitochondrial targeting by drugs and mitochondria-induced therapeutic efficacy, which may be possible to diagnose the drug efficacy to optimize the treatment for patients with cancer.