Liberating Exciton Transfer as a Pioneering Strategy to Construct Type I Photosensitizers for Hypoxia Deep-Seated Metastases Suppression

Type I photosensitizers (PSs) have revolutionized traditional photodynamic therapy for hypoxia tumors by eliminating oxygen dependence. Nevertheless, the current development of Type I PSs faces formidable obstacles stemming from the paucity of universal regulatory strategies that steer molecular systems toward efficient reactive oxygen species (ROS) generation through the Type I electron transfer pathway. Herein, we propose the "liberating exciton transfer" strategy to construct a series of Type I PSs (IDMX, X = H, F, Cl, Br) with remarkable generation of superoxide radicals (O2•–) and hydroxyl radicals (•OH). In this strategy, the halogen (F, Cl, and Br) modifications act as the "sharp hook" to release triplet excitons from their "cage", allowing them to move more freely and interact more effectively with substrates. Among them, IDMBr demonstrates superior photodynamic efficacy, enabling effective tumor cell ablation under hypoxic conditions and suppression of deep-seated pulmonary metastatic lesions and exhibiting significant clinical potential. This work establishes a novel strategy for developing Type I PSs, substantially advancing photodynamic therapy for hypoxic tumors.