Organoiridium Photosensitizers Induce Specific Oxidative Attack on Proteins within Cancer Cells

Angewandte Chemie - International Edition

4 years ago

Organoiridium Photosensitizers Induce Specific Oxidative Attack on Proteins within Cancer Cells

Huaiyi Huang, Peter J. Sadler, Hui Chao, Guy J. Clarkson, Cookson K. C. Chiu, Yuko P. Y. Lam, Pingyu Zhang, Thomas Malcomson, Abraha Habtemariam, Peter B. O'Connor, Martin J. Paterson

Strongly luminescent iridium(III) complexes, [Ir(C,N)2(S,S)]+ (1) and [Ir(C,N)2(O,O)] (2), containing C,N (phenylquinoline), O,O (diketonate), or S,S (dithione) chelating ligands, have been characterized by X-ray crystallography and DFT calculations. Their long phosphorescence lifetimes in living cancer cells give rise to high quantum yields for the generation of 1O2, with large 2-photon absorption cross-sections. 2 is nontoxic to cells, but potently cytotoxic to cancer cells upon brief irradiation with low doses of visible light, and potent at sub-micromolar doses towards 3D multicellular tumor spheroids with 2-photon red light. Photoactivation causes oxidative damage to specific histidine residues in the key proteins in aldose reductase and heat-shock protein-70 within living cancer cells. The oxidative stress induced by iridium photosensitizers during photoactivation can increase the levels of enzymes involved in the glycolytic pathway. In for a shock: A highly luminescent organoiridium complex generates 1O2 efficiently and oxidizes specific residues of heat-shock protein-70 and aldose reductase within cancer cells. The oxidative stress induced by iridium photosensitizers during photoactivation can increase the levels of the enzymes involved in the glycolytic pathway.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/anie.201709082