Photostable\nIridium(III) Cyclometallated Complex is\nan Efficient Photosensitizer for Killing Multiple Cancer Cell Lines\nand 3D Models under Low Doses of Visible Light

Photodynamic therapy delivers more targeted cell killing\nthan classical\nchemotherapy. It uses light-absorbing compounds, photosensitizers\n(PSs), to generate lethal reactive oxygen species (ROS) at sites of\nlocalized irradiation. Transition metal complexes are attractive PSs\ndue to their photostability, visible-light absorption, and high ROS\nyields. Here, we introduce a low-molecular weight, photostable iridium\ncomplex, [Ir(thpy)<sub>2</sub>(benz)]Cl, <b>1</b>, that localizes\nto the Golgi apparatus, mitochondria, and endoplasmic reticulum, absorbs\nvisible light, phosphoresces strongly, generates <sup>1</sup>O<sub>2</sub> with 43% yield, and undergoes cellular elimination after\n24 h. <b>1</b> shows low dark toxicity and under remarkably\nlow doses (3 min, 20–30 mJ s<sup>–1</sup> cm<sup>–2</sup>) of 405 or 455 nm light, it causes killing of bladder (EJ), malignant\nmelanoma (A375), and oropharyngeal (OPSCC72) cancer cells, with high\nphototoxic indices > 100–378. <b>1</b> is also an\nefficient\nPS in 3D melanoma spheroids, with repeated short-time irradiation\ncausing cumulative killing.