School of Medicine and Population Health, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, U.K.
Department of Chemistry, University of Sheffield, Sheffield S3 7HF, U.K.
J Med Chem. 2024 Sep 26;67(18):16157-16164. doi: 10.1021/acs.jmedchem.4c00869. Epub 2024 Sep 4.
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)(benz)]Cl, , that localizes to the Golgi apparatus, mitochondria, and endoplasmic reticulum, absorbs visible light, phosphoresces strongly, generates O with 43% yield, and undergoes cellular elimination after 24 h. shows low dark toxicity and under remarkably low doses (3 min, 20-30 mJ s cm) 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. is also an efficient PS in 3D melanoma spheroids, with repeated short-time irradiation causing cumulative killing.
光动力疗法比传统化疗更能靶向杀死细胞。它使用光吸收化合物，即光敏剂（PS），在局部照射部位产生致命的活性氧（ROS）。过渡金属配合物因其光稳定性、可见光吸收和高 ROS 产率而成为有吸引力的 PS。在这里，我们引入了一种低分子量、光稳定的铱配合物[Ir(thpy)(benz)]Cl，它定位于高尔基体、线粒体和内质网，吸收可见光，强烈磷光，产生活性氧（O）的产率为 43%，并在 24 小时后被细胞消除。该配合物显示出低暗毒性，在低剂量（3 分钟，20-30 mJ s cm）的 405 或 455nm 光下，它导致膀胱（EJ）、恶性黑色素瘤（A375）和口咽（OPSCC72）癌细胞的杀伤，具有高光毒性指数>100-378。该配合物也是 3D 黑色素瘤球体中的一种有效 PS，重复短时间照射会导致累积杀伤。
