Molecularly Engineered Near-Infrared Aggregation-Induced Emission Photosensitizer for In Situ-Activated Light Irradiation-Free Photodynamic Therapy
Jipeng Ding, Tianyu Zhu, Feng Bin, Fan Zheng, Shuai Huang, Fei Chen, Jie Dong, Wenbin Zeng
Abstract
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.