Sonodynamic therapy (SDT) offers distinct advantages for deep tumor ablation due to its excellent tissue penetration ability and demonstrates significant clinical potential. However, its therapeutic effectiveness is limited by the sonosensitizer's capacity to produce reactive oxygen species (ROS). In this study, an iridium(III) complex (Ir-1) was designed and evaluated as an potential SDT anticancer agent. Ir-1 exhibits a long triplet excited state lifetime of 2.57 μs and demonstrates efficient ROS generation under ultrasound (US) irradiation, with a rate constant of 0.041 min−1 for 1,3-diphenylisobenzofuran (DPBF) oxidation, which is significantly higher than that of the classic sonosensitizer Ru(bpy)3Cl2. Mechanistic studies show that while generating ROS, Ir-1 can deplete intracellular glutathione (GSH), induce lipid peroxidation, and trigger ferroptosis. In mouse tumor models, this complex exhibits significant inhibitory effects on tumor proliferation. This study provides a crucial research foundation for the application of noble metal complexes in tumor SDT.
