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

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• 作者：Luke K. McKenzie ; Dr. Igor V. Sazanovich ; Dr. Elizabeth Baggaley ; Dr. Mickaë ; le Bonneau ; Dr. Vé ; ronique Guerchais ; Prof. J. A. Gareth Williams ; Prof. Julia A. Weinstein and Dr. Helen E. Bryant
• 刊名：Chemistry - A European Journal
• 出版年：2017
• 出版时间：January 5, 2017
• 年：2017
• 卷：23
• 期：2
• 页码：234-238
• 全文大小：4508K
• ISSN：1521-3765

文摘

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.