biostudies-literatureChen Fthe 551 Health Talent Training Project of Health Commission of Zhejiang Provincethe Research Funds of Hangzhou Institute for Advanced Studythe Joint Research Program of Eye Research CenterNatural Science Foundation of Zhejiang Province, Chinathe Key Research and Development Program of Zhejiang ProvinceNational Natural Science Foundation of ChinaNational Key Research and Development Programthe Qiantang Interdisciplinary Research GrantNational Key Research and Development Program of Chinae04851https://www.ebi.ac.uk/biostudies/studies/S-EPMC12442674biostudies-literatureUnknown12(34)Pyroptosis is a proinflammatory programmed cell death (PCD) that is causally linked to antitumor immune responses, but the therapeutic potential of pyroptosis has been limited by the lack of tumor-specific and controllable inducers. Here, it is reported that tumor-specific pyroptosis can be spatiotemporally triggered via near-infrared light (NIR-pyroptosis) by using an antibody-bound indocyanine green (ICG), a clinically approved and nontoxic fluorescent dye. Mechanistically, the key molecular steps are identified by which antibody-bound ICG generates excessive reactive oxygen species (ROS) within lysosomes after internalization, leading to lysosomal membrane damage and the cytosolic release of cathepsin S (CTSS), which cleaves gasdermin D (GSDMD), IL-18, and IL-1β independently of caspaseAdvanced science (Weinheim, Baden-Wurttemberg, Germany)Lysosomal Cathepsin S Escape Facilitates Near Infrared Light-Triggered Pyroptosis Via an Antibody-Indocyanine Green Conjugate.PMC1244267482202231ERC2024014823737822024HIAS-V008T218810282172598LZ22H310001923530002024SDYXS00012023YFC3404003Shimura TCao JLu YChen FZheng WHTian XFLi XFGuo PFang MYTan WHJi QDai YJSha CLChen HBFang JMYang TChen DYShang JBfalseLysosomal Cathepsin S Escape Facilitates Near Infrared Light-Triggered Pyroptosis Via an Antibody-Indocyanine Green Conjugate.Pyroptosis is a proinflammatory programmed cell death (PCD) that is causally linked to antitumor immune responses, but the therapeutic potential of pyroptosis has been limited by the lack of tumor-specific and controllable inducers. Here, it is reported that tumor-specific pyroptosis can be spatiotemporally triggered via near-infrared light (NIR-pyroptosis) by using an antibody-bound indocyanine green (ICG), a clinically approved and nontoxic fluorescent dye. Mechanistically, the key molecular steps are identified by which antibody-bound ICG generates excessive reactive oxygen species (ROS) within lysosomes after internalization, leading to lysosomal membrane damage and the cytosolic release of cathepsin S (CTSS), which cleaves gasdermin D (GSDMD), IL-18, and IL-1β independently of caspase2025-01-01T00:00:00Z2025 Sep2026-06-03T12:09:24.129Z2026-04-27T03:11:30.666ZS-EPMC124426744053982810.1002/advs.202504851