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

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.