Light Switchable Ir(III)-Based Photosensitizers: A Dual-State System for Non-Invasive, Reversible ROS Control in Tumor Therapy

Photodynamic therapy (PDT), a powerful anticancer approach converting oxygen to ROS for tumor ablation, encounters hurdles like limited spatio-temporal selectivity, and the consequent unnecessary damage to normal tissues. Addressing these challenges, developing controllable Ir(III)-based photosensitizers (PSs) emerges as a promising solution, offering enhanced efficacy and precision in cancer therapy, while propelling the clinical progression of metal-based PSs. Herein, we proposed a series of light-controlled PSs, integrating Ir(III)-based moiety with a light-responsive module, enabling non-invasive "off-on" control of ROS production via efficient energy transfer. The open form (OF) in this dual-state system has better lipid solubility and cellular uptake compared to the closed form (CF), which facilitates targeted delivery of metal drugs. Comprehensive intracellular experiments demonstrated the OF complex's superior cytotoxicity under light irradiation, with the CF complex achieving comparable toxicity post-conversion. Notably, the PSs inhibited 3D tumor growth and modulated intracellular ROS production. These findings underscore the potential of Ir(III)-based dual-state photoswitchable complexes as a platform for non-invasive, reversible ROS control, offering broad prospects in tumor therapy and beyond.