Reactive oxygen species and glutathione dual responsive nanoparticles for enhanced prostate cancer therapy

Abstract

Docetaxel (DTX)-based chemotherapy of prostate cancer is still confronted with significant challenges due to insufficient drug accumulation at the tumor sites and the systemic side effects on normal cells and organs. Tumor microenvironment-responsive nanosized drug delivery systems have shown enormous potential to improve the anticancer efficacy and minimize the systemic side effects of chemotherapeutics. However, most of the currently redox-responsive nanoparticles respond only to single stimuli, which compromise the treatment effect. Hence, inspired by the abundance of reactive oxygen species (ROS) and intracellular glutathione (GSH) in cancer cells, we proposed a unique ROS and GSH dual responsive nanocarrier (PCL-SS) for DTX delivery. The DTX-loaded PCL-SS nanoparticles (PCL-SS@DTX NPs) were not only stable in a normal physiological environment but also rapidly triggered DTX release in prostate cancer cells. In vitro experiments showed that PCL-SS@DTX NPs had robust prostate cancer cell cytotoxicity, induced cell apoptosis, inhibited cell migration and invasion and exhibited satisfactory biocompatibility. In mice bearing orthotopic prostate cancer, PCL-SS@DTX NPs could accumulate in orthotopic tumor sites and then significantly weaken tumor growth by inhibiting prostate cancer cell proliferation and inducing cell apoptosis, without obvious damages to major organs. Overall, this dual responsive nanosized drug delivery system may act as a promising therapeutic option for prostate cancer chemotherapy.