Intracellularly acid-switchable multifunctional micelles for combinational photo/chemotherapy of the drug-resistant tumor

The intrinsic or acquired drug resistance is the main challenge for cancer chemotherapy today. So far, many nanosized drug delivery systems (NDDS) have been exploited to combat cancer drug resistance. However, the therapy efficacy of current NDDS is severely impaired by the limited tumor penetration of the nanoparticles due to the existence of physiological and pathological barriers in the solid tumor. In this study, we report on the design and fabrication of intracellularly acid-switchable multifunctional micelles for combinational photo- and chemotherapy of the drug-resistant tumor. The micelles were composed of a pH-responsive diblock copolymer, a photosensitizer, and a polymeric prodrug of doxorubicin. The micelle displayed silenced fluorescence and photoactivity during the blood circulation and switched to an active state in weakly acid conditions (i.e., p