A mitochondrial-targeting and NO-based anticancer nanosystem with enhanced photo-controllability and low dark-toxicity

Abstract

Compared to the generation of singlet oxygen in photodynamic therapy, photo-generation of nitric oxide (NO) would not be limited by the concentration of molecular oxygen. However, therapeutic applications of exogenous nitric oxide are usually limited by its short half-life and its vulnerability to many biological substances, thus straightforward and precise control over NO delivery may be critical to its therapeutic effects. Herein, we demonstrate a mitochondrial-targeting and photoactive NO-releasing system as an anticancer drug. Fabricated by covalently incorporating a photo-responsive NO-donor and a mitochondrial targeting ligand onto carbon dots, this nanosystem exhibits a multi-functional nature which combines mitochondrial-targeting, photocontrollable NO-releasing and cell imaging. Upon cellular internalization, the nanosystem could target mitochondria effectively. Furthermore, the system displays little dark toxicity under physiological temperature; but upon light irradiation, it could release NO, efficiently damage mitochondria and consequently cause prominent apoptosis of cancer cells. Moreover, evaluated by using MTT assay, this nanosystem shows high cytotoxicity towards two cancer cell lines. These observations provide new insights for exploiting NO in disease therapy.