Targeted Photoredox System under a Hypoxic Environment to Evoke Photodynamic Immunotherapy
Na Xu1, Hongbao Fang1, Zhirong Zhu1
1Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, Nanjing Drum Tower Hospital, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China.
Abstract:
Conventional oxygen dependent type-II photodynamic therapy (PDT) was significantly constrained by the hypoxic tumor microenvironment. Type-I photosensitizers (PSs) produce oxygen radicals through the electron transfer (ET) pathway and are less oxygen dependent. However, no proven design strategy for generic Type-I PSs has been clarified. In this work, type-I PS BDP-Ir-bpt has been successfully synthesized, with the modification of triplet state energy via ligand upgradation. Under hypoxia with 630 nm irradiation with PS BDP-Ir-bpt, the intracellular photoredox system was disrupted and intracellular O2-• and •OH were significantly produced. Oxygen radicals further ruptured the lysosomal membrane, releasing cathepsin B and inducing GSDMD-mediated pyroptosis. Subsequently, the innate immune responses were evoked, as observed in an in vivo mouse prophylactic model. This work not only provided a biocompatible photosensitizer to relieve the hypoxic microenvironment and initiate photodynamic immunotherapy but also demonstrated the importance of the rational structural design for cancer therapy.
