Aggregation-induced emission sonosensitizers: molecular engineering and biomedical applications

Sonodynamic therapy (SDT) has emerged as a promising modality for biomedical applications owing to its non-invasive nature, deep tissue penetration and precise spatiotemporal controllability. However, the clinical potential of conventional sonosensitizers remains limited for their low reactive oxygen species (ROS) generation efficiency, poor physicochemical stability and suboptimal biocompatibility. Aggregation-induced emission (AIE) sonosensitizers have recently gained great attention as a transformative class of materials capable of overcoming these constraints through their unique molecular conformations and photophysical properties. This review provides a comprehensive overview of recent advances in AIE sonosensitizers, systematically classifying them into small molecules (D–A, D–A–D, A–D–A′ structures, and metal complexes) and polymers. We particularly emphasize molecular engineering strategies, such as modulating donor–acceptor interaction, π-conjugated bridges, and heavy atom effects that enhance intersystem crossing efficiency and narrow singlet–triplet energy gaps, thereby boosting the sono-induced ROS generation ability. Furthermore, we highlight their versatile biomedical functionalities, including high-contrast image-guided SDT, hypoxia-adaptable therapy, and integration into multimodal treatment regimens such as immunotherapy, gas therapy and thrombolysis. Finally, we discuss the persisting challenges and translational prospects of AIE sonosensitizers. This review will provide new insights into the design of organic sonosensitizers to realize maximized effectiveness in biomedical fields.