Binary dimeric prodrug nanoparticles for self-boosted drug release and synergistic chemo-photodynamic therapy

Abstract

Chemotherapy is the major strategy for cancer therapy, but its limited therapeutic efficiency and serious toxicity to normal tissues greatly restrict its clinical performance. Herein, we develop carrier-free self-activated prodrug nanoparticles combining chemotherapy and photodynamic therapy to enhance the antitumor efficiency. Reactive oxygen species (ROS)-responsive paclitaxel and porphyrin prodrugs are synthesized and co-assembled into nanoparticles without the addition of any adjuvants, which improves the drug content and reduces carrier-associated toxicity. After entering cancer cells, the obtained co-assembled nanoparticles can generate sufficient ROS upon light irradiation not only for photodynamic therapy, but also triggering on-demand drug release for chemotherapy, thus realizing self-enhanced prodrug activation and synergistic chemo-photodynamic therapy. This simple and effective carrier-free prodrug nanoplatform unifies the distinct traits of on-demand drug release and combination therapy, thus possessing great potential in advancing cancer treatment.