Molecular Design Strategy for Iridium(Ⅲ)-based Photosensitizers to Enhance the Phototoxicity Index and Efficacy of Photodynamic Therapy

In photodynamic therapy (PDT), the phototoxicity index (PI) is crucial for evaluating photosensitizer (PS) efficiency, with dark toxicity lowering PI and increasing side effects. Ir(III)-based PSs effectively generate ROS, but some exhibit high dark toxicity, reducing PDT efficacy. Here, we propose a molecular design strategy to mitigate dark toxicity and enhance phototoxicity by modulating charge and incorporating organelle-targeting groups. Our results show that neutrally charged PSs exhibit lower dark toxicity than positively charged PSs, while organelle-targeting modifications enhance phototoxicity. This study highlights the importance of optimizing molecular charge and targeting properties to maximize PDT effectiveness.