用于硫化氢（H2S）检测和缺氧肿瘤光动力治疗（PDT）的多功能I型光敏剂（PSs）表现出诱人的疗效，但仍然是一项具有挑战性的任务。在此，设计并合成了一种线粒体靶向聚集诱导发射（AIE）光敏剂TSPy-SS-P，可用于H2S检测和同时I型和II型PDT。 TSPy-SS-P对肿瘤细胞内源性和外源性H2S检测具有优异的选择性和抗干扰能力。 TSPy-SS-P 能够通过对 H2S 的荧光“关闭”反应来区分具有高水平 H2S 的肿瘤细胞和正常细胞。此外，TSPy-SS-P表现出Ⅰ型和Ⅱ型活性氧（ROS）生成能力，可有效消融缺氧的肿瘤细胞。 TSPy-SS-P表现出线粒体靶向能力，可以原位产生ROS破坏线粒体并促进细胞凋亡。体内PDT实验表明TSPy-SS-P具有优异的肿瘤保留能力、有效的肿瘤消融能力和良好的生物相容性。这项工作提供了一种双管齐下的策略来设计用于 H2S 检测和有效肿瘤 PDT 的细胞器靶向光敏剂。版权所有 © 2024 Elsevier B.V. 保留所有权利。

Multifunctional type-I photosensitizers (PSs) for hydrogen sulfide (H2S) detection and photodynamic therapy (PDT) of hypoxia tumors exhibits attractive curative effect but remains a challenging task. Herein, a mitochondria targeted aggregation-induced emission (AIE) photosensitizer TSPy-SS-P was designed and synthesized, which could be used for H2S detection and simultaneously type I and type II PDT. TSPy-SS-P had excellent selectivity and anti-interference abilities for endogenous and exogenous H2S detection in tumor cells. TSPy-SS-P was able to distinguish tumor cells with high level of H2S from normal cells by fluorescence "turn off" response to H2S. In addition, TSPy-SS-P showed type Ⅰ and type Ⅱ reactive oxygen species (ROS) generation ability to effectively ablate hypoxic tumor cells. TSPy-SS-P showed mitochondria targeting capacity which could produce ROS in situ to disrupt mitochondria and promote cell apoptosis. In vivo PDT experiments showcased that TSPy-SS-P had excellent tumor retention capability, effective tumor ablation ability and good biocompatibility. This work provided a two-pronged strategy to design organelles targeted photosensitizers for H2S detection and effective PDT of tumors.Copyright © 2024 Elsevier B.V. All rights reserved.