Photostable Iridium(III) Cyclometallated Complex is an Efficient Photosensitizer for Killing Multiple Cancer Cell Lines and 3D Models under Low Doses of Visible Light

Photodynamic therapy delivers more targeted cell killing
than classical
chemotherapy. It uses light-absorbing compounds, photosensitizers
(PSs), to generate lethal reactive oxygen species (ROS) at sites of
localized irradiation. Transition metal complexes are attractive PSs
due to their photostability, visible-light absorption, and high ROS
yields. Here, we introduce a low-molecular weight, photostable iridium
complex, [Ir(thpy)2(benz)]Cl, 1, that localizes
to the Golgi apparatus, mitochondria, and endoplasmic reticulum, absorbs
visible light, phosphoresces strongly, generates 1O2 with 43% yield, and undergoes cellular elimination after
24 h. 1 shows low dark toxicity and under remarkably
low doses (3 min, 20–30 mJ s–1 cm–2) of 405 or 455 nm light, it causes killing of bladder (EJ), malignant
melanoma (A375), and oropharyngeal (OPSCC72) cancer cells, with high
phototoxic indices > 100–378. 1 is also an
efficient
PS in 3D melanoma spheroids, with repeated short-time irradiation
causing cumulative killing.