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Life sciences · Journal article
Acs Applied Materials & Interfaces · September 19, 2026
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Abstract Sonodynamic therapy (SDT) is an emerging noninvasive treatment for tumors with the advantage of deep tissue penetration. However, it is still challenging to develop effective organic sonosensitizers with good stability for imaging and SDT. In this work, in order to reveal the structure–activity relationship of sonosensitizers, we designed and synthesized a series of aza-BODIPY derivatives (AB1–AB5) with different substituents (methoxy, octyloxy, anthracene, and iodine atom) to systematically evaluate the influence of electron-donating effect and heavy atom effect on the sonodynamic efficacy. Among them, the iodine-substituted aza-BODIPY (AB5) demonstrated superior sonodynamic performance and exhibited enhanced reactive oxygen species (ROS) generation. Subsequently, we encapsulated AB5 with the hydrophilic polymer DSPE-mPEG2000 to create nanoparticles referred to as iodinated aza-BODIPY nanoparticles (IABNPs). In vitro cellular assays and in vivo animal experiments showed that IABNPs had excellent stability, biocompatibility, and pronounced sonodynamic effect, which resulted in significant inhibition of tumor growth. Moreover, the fluorescent emission characteristics of AB5 enabled fluorescence-guided imaging and real-time monitoring during tumor treatment. This study systematically explored the influence of substituents on the sonodynamic effect of aza-BODIPY, providing important theoretical foundations and perspectives for future research in related fields.