The Affiliated Xiangshan Hospital of Wenzhou Medical University: Xiangshan First People's Hospital Medical and Health Group, Xiangshan, 315700, China.
School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China; Huadu District People's Hospital, Southern Medical University, Guangzhou, Guangdong, 510530, China.
Talanta. 2025 Jan 1;282:127074. doi: 10.1016/j.talanta.2024.127074. Epub 2024 Oct 18.
Multifunctional type-I photosensitizers (PSs) for hydrogen sulfide (HS) 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 HS detection and simultaneously type I and type II PDT. TSPy-SS-P had excellent selectivity and anti-interference abilities for endogenous and exogenous HS detection in tumor cells. TSPy-SS-P was able to distinguish tumor cells with high level of HS from normal cells by fluorescence "turn off" response to HS. 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 HS detection and effective PDT of tumors.
多功能 I 型光动力治疗(PDT)敏化剂(PSs)用于检测硫化氢(HS)和缺氧肿瘤的 PDT 具有诱人的疗效,但仍然是一项具有挑战性的任务。本文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,它可用于 HS 检测和 I 型和 II 型 PDT。TSPy-SS-P 对肿瘤细胞内源性和外源性 HS 检测具有优异的选择性和抗干扰能力。TSPy-SS-P 能够通过荧光“关闭”响应 HS 来区分 HS 水平高的肿瘤细胞与正常细胞。此外,TSPy-SS-P 表现出 I 型和 II 型活性氧(ROS)生成能力,可有效消融缺氧肿瘤细胞。TSPy-SS-P 具有线粒体靶向能力,可原位产生 ROS 以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设计针对 HS 检测和有效 PDT 的细胞器靶向光敏剂的双重策略。