Molecularly Engineered Near-Infrared Aggregation-Induced Emission Photosensitizer for In Situ-Activated Light Irradiation-Free Photodynamic Therapy

Conventional photodynamic therapy (PDT) suffers from limited efficacy in treating solid tumors due to the poor penetration depth of light. Chemiluminescence-guided PDT emerges as a promising alternative, offering irradiation-free excitation and localized activation for precise tumor targeting. Herein, we report the development of a novel Type-I photosensitizer, DCzIBr, constructed by molecular engineering. DCzIBr exhibits near-infrared (NIR) emission and robust superoxide radical generation. DCzIBr and CPPO were co-encapsulated within F127 micelles to form DCzIBr-C nanoparticles (DCzIBr-C NPs), which can be selectively activated by hydrogen peroxide, leading to long-lived NIR chemiluminescence and sustained superoxide radical generation. Notably, the exclusive superoxide radical generation by DCzIBr facilitates a unique recycling mechanism for partial oxygen and hydrogen peroxide within the chemiluminescence-PDT system. In vitro studies demonstrated the light irradiation-free selective killing of tumor cells by DCzIBr-C NPs. Furthermore, successful in vivo antitumor assays highlight the potential of chemiluminescence-PDT for tumor theranostics. This work presents a novel paradigm for constructing irradiation-free PDT based on Type-I photosensitizers.