Iridium complex-based ferroptosis inducer for cancer sonodynamic therapy

Abstract

Sonodynamic therapy (SDT) offers distinct advantages for deep tumor ablation due to its excellent tissue penetration ability and demonstrates significant preclinical and clinical potential. However, its therapeutic effectiveness is frequently limited by the sonosensitizer's restricted ability to produce reactive oxygen species (ROS). In this study, we designed an iridium(III) complex to evaluate its potential as an SDT anticancer agent. Ir-1 has a relatively long triplet excited state lifetime of 2.57 μs. This sonosensitizer demonstrated efficient ROS generation under ultrasound (US) irradiation, with a rate constant for DPBF oxidation of 0.04081 min-1, which is higher than that of Ru(bpy)3Cl2. It exhibits high sonocytotoxicity and effectively inhibits tumor growth in 4T1 cells. Additionally, it demonstrated favorable biocompatibility. This work provides valuable insights into the design of first-row transition metal complexes for SDT applications and enhances our understanding of the regulatory mechanisms of iridium complexes as sonosensitizers.