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-PEG 2000 , 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. • A benzothiadiazole-based sonosensitizer with A-π-D-π-A conjugation shows AIE feature and strong NIR-II fluorescence. • NP BBTPA nanoparticles enable efficient ROS generation under ultrasound and ROS-responsive dissociation. • Ultrasound-activated NP BBTPA induces mitochondrial damage, triggers pyroptosis and immunogenic cell death (ICD). • In vivo studies reveal 70.5% tumor growth inhibition with 1.9-fold increased CD8 + T cell infiltration. • The integrated theranostic platform shows great potential for bladder cancer therapy.