Metal Complexes for Two-Photon Photodynamic Therapy: A Cyclometallated Iridium Complex Induces Two-Photon Photosensitization of Cancer Cells under Near-IR Light

McKenzie, L.K.; Sazanovich, I.V.; Baggaley, E.; Bonneau, M.; Guerchais, V.; Williams, J.A.G.; Weinstein, J.A.; Bryant, H.E.

Abstract

Photodynamic therapy (PDT) uses photosensitizers (PS) which only become cytotoxic upon light-irradiation. Transition-metal complexes are highly promising PS due to long excited-state lifetimes, and high photo-stabilities. However, these complexes usually absorb higher-energy UV/Vis light, whereas the optimal tissue transparency is in the lower-energy NIR region. Two-photon excitation (TPE) can overcome this dichotomy, with simultaneous absorption of two lower-energy NIR-photons populating the same PS-active excited state as one higher-energy photon. We introduce two low-molecular weight, long-lived and photo-stable iridium complexes of the [Ir(N^C)2(N^N)]+ family with high TP-absorption, which localise to mitochondria and lysosomal structures in live cells. The compounds are efficient PS under 1-photon irradiation (405 nm) resulting in apoptotic cell death in diverse cancer cell lines at low light doses (3.6 J cm−2), low concentrations, and photo-indexes greater than 555. Remarkably 1 also displays high PS activity killing cancer cells under NIR two-photon excitation (760 nm), which along with its photo-stability indicates potential future clinical application.

Citation

McKenzie, L., Sazanovich, I., Baggaley, E., Bonneau, M., Guerchais, V., Williams, J., …Bryant, H. (2017). Metal Complexes for Two-Photon Photodynamic Therapy: A Cyclometallated Iridium Complex Induces Two-Photon Photosensitization of Cancer Cells under Near-IR Light. Chemistry - A European Journal, 23(2), 234-238. https://doi.org/10.1002/chem.201604792

• Journal Article Type: Article
• Acceptance Date: Oct 13, 2016
• Online Publication Date: Nov 2, 2016
• Publication Date: Jan 5, 2017
• Deposit Date: Mar 17, 2017
• Publicly Available Date: Mar 28, 2017
• Journal: Chemistry - A European Journal
• Print ISSN: 0947-6539
• Electronic ISSN: 1521-3765
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 23
• Issue: 2
• Pages: 234-238
• DOI: https://doi.org/10.1002/chem.201604792
• Public URL: https://durham-repository.worktribe.com/output/1360989