Exploring BODIPY derivatives as sonosensitizers for anticancer sonodynamic therapy

Sonodynamic therapy (SDT) is an emerging non-invasive and effective therapeutic modality for cancer treatment bearing benefit of deep tissue-penetration in comparison to photo-inspired therapy. However, exploring novel sonosensitizers with high sonosensitivity and desirable biosafety remains a significant challenge. Although boron dipyrromethene (BODIPY) dyes have been widely used in biomedical filed, no BODIPY-based sonosensitizers have been reported yet. Herein, we synthesized four BODIPY dyes (BDP1-BDP4) and investigated their potential applications in SDT. BDP4 exhibited superb sonosensitivity and high SDT efficiency against cancer cells and tumors in tumor-bearing mice. The types of the generated reactive oxygen species, cavitation effect, and cell apoptosis were investigated to figure out the sonodynamic therapeutic mechanisms of BDP4. This work for the first time demonstrates the potential of BODIPY dyes as novel sonosensitizers for SDT, which may pave an avenue for developing more efficient and safer sonosensitizers in future.