A hypochlorite-activated strategy for realizing fluorescence turn-on, type I and type II ROS-combined photodynamic tumor ablation

The combination of cancer cell-activated fluorescence and the advantages of both type I and type II photodynamic therapy (PDT) capabilities to achieve a synergistic therapeutic effect in a complex tumor environment is highly desirable. Herein, we report an approach by means of tumor intracellular hypochlorite (ClO−) to turn on fluorescence integrated with type I and II ROS generation for imaging-guided PDT. The resultant PTZSPy functions as a type II photosensitizer with mitochondria-targeting capability. In the presence of ClO−, PTZSPy is transformed into its oxidized counterpart SPTZSPy, turns on an orange-red fluorescence and triggers the type I ROS generation ability. Biological studies revealed that PTZSPy can accurately distinguishes tumor cells from normal cells, dynamically monitors the cell ablation process and be utilized for theranostics in MCF-7 tumor-bearing nude mice in vivo. This work provides an innovative strategy exploiting the highly abundant ClO− in tumor cells for the type I and II ROS two-pronged and imaging-guided PDT.