A Novel BODIPY-Zn Complex as Innovative Sonosensitizer for Enhanced Sonodynamic Therapy

Ultrasound (US)-based sonodynamic therapy (SDT) presents a promising and secure approach to treating cancer with the advantage of enhanced tissue penetration, making it a favorable option compared with traditional photodynamic therapy. However, the search for innovative sonosensitizers that exhibit both high sonosensitizing efficacy and good biocompatibility poses a formidable challenge. In this research, we prepared a novel BODIPY-Zn complex (<b>BSS-Zn</b>) incorporating a hydrophilic short polyethylene glycol unit and explored its feasibility as a sonosensitizer. <b>BSS-Zn</b> exhibited enhanced reactive oxygen species (ROS) generation behavior upon US irradiation, outperforming a control sensitizer, <b>BSS</b> (an analog lacking the Zn complex), and a commercial sonosensitizer, ZnPc (currently undergoing clinical testing), with regard to sonosensitizing properties. The enhanced effect of <b>BSS-Zn</b> was attributed to increased levels of ROS, such as hydroxyl radicals, singlet oxygen, and superoxide, mediated by US exposure in aqueous media. The SDT effect of <b>BSS-Zn</b> on MDA-MB-231 cells was verified by confirming the intracellular types of generated ROS and evaluating the cytotoxicity to MDA-MB-231 cancer cells. This pioneering study highlights the potential of <b>BSS-Zn</b> as an innovative sonosensitizer for SDT. Our findings provide valuable guidance for the design of efficient sonosensitizers.