Metal Complexes For Two-photon Photodynamic Therapy: A Cyclometallated Iridium Complex Induces Two-photon Photosensitization of Cancer Cells Under Near-IR Light.

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 photostability. However, these complexes usually absorb higher-energy UV/Visible light, whilst 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 photostable 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 photoindexes of up to >555. Remarkably 1 also displays high PS activity killing cancer cells under NIR two-photon excitation (760 nm), which along with its photostability indicates potential future clinical application.