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

J Med Chem. 2024 Sep 26;67(18):16157-16164. doi: 10.1021/acs.jmedchem.4c00869. Epub 2024 Sep 4.

Abstract

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.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Coordination Complexes* / chemical synthesis
  • Coordination Complexes* / chemistry
  • Coordination Complexes* / pharmacology
  • Coordination Complexes* / radiation effects
  • Humans
  • Iridium* / chemistry
  • Iridium* / pharmacology
  • Light*
  • Photochemotherapy*
  • Photosensitizing Agents* / chemical synthesis
  • Photosensitizing Agents* / chemistry
  • Photosensitizing Agents* / pharmacology
  • Reactive Oxygen Species / metabolism

Substances

  • Photosensitizing Agents
  • Iridium
  • Coordination Complexes
  • Antineoplastic Agents
  • Reactive Oxygen Species