A Photo-Activated Continuous Reactive Oxygen Species Nanoamplifier for Dual-Dynamic Cascade Cancer Therapy

The special redox homeostasis of tumor cells makes reactive oxygen species (ROS)-based approaches a promising cancer therapeutic strategy. Among these approaches, photodynamic therapy is the most widely studied ROS-based treatment due to its ability to achieve targeted therapy by local light irradiation. However, achieving efficient and continuous ROS generation without prolonged laser exposure is still challenging. In this work, a photo-activated continuous ROS nanoamplifier is proposed for photodynamic-chemodynamic cascade therapy. Upon local laser irradiation, the nanoamplifier can continuously amplify cellular oxidative stress through a positive feedback loop of "light-triggered ROS generation, ROS-responsive prodrug activation, and Fenton reaction-mediated ROS cyclic regenerative amplification", avoiding tissue damage caused by excessive laser exposure. This strategy provides a potential pathway to overcome the limitations of ROS-based therapeutic approaches.