ROS-responsive polyprodrug micelles carrying suicide genes in combination with chemotherapy and gene therapy for prostate cancer treatment

Abstract

Prostate cancer is the most common malignant tumor in the male reproductive system, and its incidence increases with age. Chemotherapy is one of the main strategies for treating prostate cancer, but it often comes with unavoidable side effects. Nanocarriers can improve drug utilization and targeting, and cationic carriers can also carry nucleic acids for gene therapy. In this study, we prepared a cationic micelle constructed from a polyprodrug that can deliver both chemotherapeutic drugs and nucleic acids simultaneously. The typical chemotherapeutic drug hydroxycamptothecin (HCPT) was linked by reactive oxygen species (ROS)-responsive coupling agents and forms amphiphilic block polymers with low molecular weight polyethyleneimine (PEI). The resulting cationic micelles can be triggered by high levels of ROS in tumor cells and collapse to release HCPT and suicide genes to kill tumor cells. At the same time, it reduces the killing of normal cells. In prostate cancer cells, it has been confirmed that the co-delivery carriers combined with chemotherapy and a suicide gene prodrug system have shown an ideal therapeutic effect on prostate cancer.