A highly potent ruthenium(II)-sonosensitizer and sonocatalyst for in vivo sonotherapy

As a basic structure of most polypyridinal metal complexes, [Ru(bpy)(3)](2+), has the advantages of simple structure, facile synthesis and high yield, which has great potential for scientific research and application. However, sonodynamic therapy (SDT) performance of [Ru(bpy)(3)](2+) has not been investigated so far. SDT can overcome the tissue-penetration and phototoxicity problems compared to photodynamic therapy. Here, we report that [Ru(bpy)(3)](2+) is a highly potent sonosensitizer and sonocatalyst for sonotherapy in vitro and in vivo. [Ru(bpy)(3)](2+) can produce singlet oxygen (O-1(2)) and sono-oxidize endogenous 1,4-dihydronicotinamide adenine dinucleotide (NADH) under ultrasound (US) stimulation in cancer cells. Furthermore, [Ru(bpy)(3)](2+) enables effective destruction of mice tumors, and the therapeutic effect can reach deep tissues over 10 cm under US irradiation. This work paves a way for polypyridinal metal complexes to be applied to the noninvasive precise sonotherapy of cancer. Sonodynamic therapy has therapeutic promise due to its safety and good tissue penetration, but is currently bottlenecked due to a lack of efficient and safe sonosensitizers. Here the authors show that [Ru(bpy)(3)](2+) can produce singlet oxygen and sonooxidize NADH in deep tissue, and destroy mouse tumors effectively.

Automated summary

This study demonstrates that [Ru(bpy)(3)](2+) can serve as a highly efficient sonosensitizer and sonocatalyst, producing therapeutic effects in cancer cells in vitro and effectively destroying mouse tumors in vivo. The findings open up possibilities for the use of polypyridinal metal complexes in noninvasive precise sonotherapy for cancer treatment, addressing the current bottleneck of a lack of efficient and safe sonosensitizers in sonodynamic therapy.