Methods: GSH-activated photosensitizers MTP-NO2 and NTP-NO2 were synthesized based on donor-acceptor structure, with their GSH-triggered activation, GSH depletion, ROS restoration, and caspase-1/GSDMD-mediated pyroptosis systematically demonstrated in 4T1 cells, while tumor accumulation, biodistribution, in vivo activation, and photodynamic antitumor efficacy of PSs nanoparticles were comprehensively assessed in 4T1 tumor-bearing mice through fluorescence imaging and immunohistochemical analyses. This evidence concerns the gene GSDMD and neoplasm.