Zhang Li-Na, Wei Yuan-Feng, Ran Xiao-Yun, Shi Lei, Wang Zhou-Yu, Chen Shan-Yong, Yi Cheng, Yu Xiao-Qi, Li Kun
Key Laboratory of Green Chemistry and Technology of Ministry of Education, College of Chemistry, Sichuan University, Chengdu, Sichuan 610064, China.
Department of Medical Oncology, Cancer Center, West China Hospital Sichuan University Chengdu, Sichuan 610064, China.
JACS Au. 2025 Aug 7;5(8):3982-3993. doi: 10.1021/jacsau.5c00624. eCollection 2025 Aug 25.
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 (O ) 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.
I型光敏剂(PSs)通过消除对氧气的依赖性,彻底改变了传统的针对缺氧肿瘤的光动力疗法。然而,目前I型PSs的发展面临着巨大障碍,这源于缺乏通用的调控策略,无法引导分子系统通过I型电子转移途径高效产生活性氧(ROS)。在此,我们提出“释放激子转移”策略,构建了一系列能显著产生活性超氧自由基(O )和羟基自由基(•OH)的I型PSs(IDMX,X = H、F、Cl、Br)。在该策略中,卤素(F、Cl和Br)修饰充当“尖钩”,从“牢笼”中释放三线态激子,使其能够更自由地移动并与底物更有效地相互作用。其中,IDMBr展现出卓越的光动力疗效,能够在缺氧条件下有效消融肿瘤细胞、抑制深部肺转移病灶,具有显著的临床潜力。这项工作为开发I型PSs建立了一种新策略,极大地推动了针对缺氧肿瘤的光动力疗法的发展。