NIR-II aggregation-induced emission sonosensitizer for pyroptosis induction in bladder cancer

Sonodynamic therapy (SDT) represents a promising methodology that employs sonosensitizers in conjunction with low-intensity ultrasound for the eradication of malignant tumors, featuring precise treatment capabilities, deep tissue penetrability, and minimal side effects. Conventional sonosensitizers often face challenges such as aggregation-caused quenching (ACQ), which hampers the efficiency of reactive oxygen species (ROS) generation. In this study, we report a novel benzothiadiazole-based sonosensitizer derivative, BBTPA, exhibiting aggregation-induced emission (AIE) characteristics. By co-assembling BBTPA with the ROS-responsive polymer PMD and the amphiphilic polymer DSPE-PEG₂₀₀₀, we engineered BBTPA nanoparticles (NP^BBTPA). Upon ultrasound exposure, NP^BBTPA produces ROS efficiently, inducing mitochondrial damage and triggering pyroptotic cell death. Moreover, NP^BBTPA induces immunogenic cell death (ICD) under ultrasound stimulation, thus enhancing antitumor immune responses. This study extends the utility of AIE-based sonodynamic agents in efficient cancer therapy, holding promising prospects for bladder cancer treatment.