Two-pronged strategy: A mitochondria targeting AIE photosensitizer for hydrogen sulfide detection and type I and type II photodynamic therapy

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.