title: Metal Complexes for Two-Photon Photodynamic Therapy: A Cyclometallated Iridium Complex Induces Two-Photon Photosensitization of Cancer Cells under Near-IR Light.
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.
authors.affiliation: Department of Oncology and Metabolism, University of Sheffield, Sheffield, S10 2RX, UK.|Department of Chemistry, University of Sheffield, Sheffield, S3 7HF, UK.
authors.forename: Luke K
authors.initials: LK
authors.lastname: McKenzie
authors.affiliation: Department of Oncology and Metabolism, University of Sheffield, Sheffield, S10 2RX, UK.|Department of Chemistry, University of Sheffield, Sheffield, S3 7HF, UK.|Harwell Science Campus, OX11 0QX, UK.
authors.forename: Igor V
authors.initials: IV
authors.lastname: Sazanovich
authors.affiliation: Department of Chemistry, University of Sheffield, Sheffield, S3 7HF, UK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Baggaley
authors.affiliation: Department of chemistry, Durham University, Durham, DH1 3LE, UK.|UMR CNRS 6226, Université de Rennes 1, Institut des Sciences Chimiques de Rennes, Campus de Beaulieu, 35042, Rennes, France.
authors.forename: Mickaële
authors.initials: M
authors.lastname: Bonneau
authors.affiliation: UMR CNRS 6226, Université de Rennes 1, Institut des Sciences Chimiques de Rennes, Campus de Beaulieu, 35042, Rennes, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Guerchais
authors.affiliation: Department of chemistry, Durham University, Durham, DH1 3LE, UK.
authors.forename: J A Gareth
authors.initials: JA
authors.lastname: Williams
authors.affiliation: Department of Chemistry, University of Sheffield, Sheffield, S3 7HF, UK.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Weinstein
authors.affiliation: Department of Oncology and Metabolism, University of Sheffield, Sheffield, S10 2RX, UK.
authors.forename: Helen E
authors.identifier: 0000-0003-2720-7020
authors.initials: HE
authors.lastname: Bryant
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007495:Iridium / Q000737:chemistry / Q000494:pharmacology*; D008027:Light; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D026082:Singlet Oxygen / Q000378:metabolism
chemical_list: D056831:Coordination Complexes; D017319:Photosensitizing Agents; D026082:Singlet Oxygen; D007495:Iridium
keywords: cancer therapy; iridium; singlet oxygen; transition metals; two-photon photodynamic therapy