Activatable nano-photosensitizers for precise photodynamic cancer therapy

Owing to the excellent cell ablation ability and low side effects, photodynamic therapy (PDT) plays an important role in disease treatment, especially cancer. However, most PDT agents show off-target phototoxicity toward normal tissues such as skin and organs, due to deficiencies of PDT agents in specific accumulation at tumors and undesired activation of PDT agents in normal tissues. To enhance the therapeutic accuracy and reduce the side effects, great efforts have been devoted to developing activatable photodynamic nano-photosensitizers (nanoPSs) with controllable reactive oxygen species (ROS) generation in the past years. Activatable nano-PSs are responsive to tumor-associated stimuli or external stimuli, such as acidic pH, ROS, H2O2, enzymes, light and heat. These nano-PSs are in "off-state" during delivery until they are activated in targeted lesions to generate ROS under specific stimuli, which can enhance the PDT efficiency and accuracy as well as minimize the side effects. In this review, we summarize the recent works on the design, work principle, and therapeutic performance of PDT using activatable nano-PSs. The activatable nano-PSs are discussed according to the different stimuli along with different types of composite materials. Finally, we propose the current challenges and provide possible solutions for future developments of activatable PDT.