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

Shan, Meixin; Wang, Xinwei; Wang, Zhu; Xu, Chun; Li, Leijiao; Li, Wenliang; Xiao, Haihua; Wahafu, Wasilijiang · Bioact Mater · 2026

basic_science · Level V

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Abstract

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<sub>2000</sub>, we engineered BBTPA nanoparticles (NP<sup>BBTPA</sup>). Upon ultrasound exposure, NP<sup>BBTPA</sup> produces ROS efficiently, inducing mitochondrial damage and triggering pyroptotic cell death. Moreover, NP<sup>BBTPA</sup> 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.