Dinuclear Dicationic Iridium Complexes for Highly Synergistic Photodynamic and Photothermal Therapy to Chemoresistant Cancer

A series of dinuclear Ir(III) complexes have been constructed for enhanced photodynamic and photothermal therapy (PDT and PTT) for cisplatin-resistant non-small-cell lung cancer. They enter cells via caveolar endocytosis, target mitochondria but not nuclear, generate both singlet oxygen and superoxide anion, and release heat when exposed to infrared (IR) irradiation, thus inducing reactive oxygen species (ROS)-associated cell disruption and thermal ablation. The IR-generated ROS can further activate caspases, triggering apoptosis. Additionally, the ROS deplete intracellular glutathione, lead to lipid peroxidation, and induce ferroptosis. The selected dinuclear Ir(III) complex