title: Photodynamic killing of cancer cells by a Platinum(II) complex with cyclometallating ligand.
abstract: Photodynamic therapy that uses photosensitizers which only become toxic upon light-irradiation provides a strong alternative to conventional cancer treatment due to its ability to selectively target tumour material without affecting healthy tissue. Transition metal complexes are highly promising PDT agents due to intense visible light absorption, yet the majority are toxic even without light. This study introduces a small, photostable, charge-neutral platinum-based compound, Pt(II) 2,6-dipyrido-4-methyl-benzenechloride, complex 1, as a photosensitizer, which works under visible light. Activation of the new photosensitizer at low concentrations (0.1-1 μM) by comparatively low dose of 405 nm light (3.6 J cm(-2)) causes significant cell death of cervical, colorectal and bladder cancer cell lines, and, importantly, a cisplatin resistant cell line EJ-R. The photo-index of the complex is 8. We demonstrate that complex 1 induces irreversible DNA single strand breaks following irradiation, and that oxygen is essential for the photoinduced action. Neither light, nor compound alone led to cell death. The key advantages of the new drug include a remarkably fast accumulation time (diffusion-controlled, minutes), and photostability. This study demonstrates a highly promising new agent for photodynamic therapy, and attracts attention to photostable metal complexes as viable alternatives to conventional chemotherapeutics, such as cisplatin.
authors.affiliation: Academic Unit of Molecular Oncology, Department of Oncology, Sheffield Cancer Research Centre, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, United Kingdom.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Doherty
authors.affiliation: Academic Unit of Molecular Oncology, Department of Oncology, Sheffield Cancer Research Centre, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, United Kingdom.|Department of Chemistry, University of Sheffield, Sheffield S3 7HF, United Kingdom.
authors.forename: Igor V
authors.initials: IV
authors.lastname: Sazanovich
authors.affiliation: Academic Unit of Molecular Oncology, Department of Oncology, Sheffield Cancer Research Centre, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, United Kingdom.|Department of Chemistry, University of Sheffield, Sheffield S3 7HF, United Kingdom.
authors.forename: Luke K
authors.initials: LK
authors.lastname: McKenzie
authors.affiliation: Institute of Physics, Minsk, Belarus.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Stasheuski
authors.affiliation: Academic Unit of Molecular Oncology, Department of Oncology, Sheffield Cancer Research Centre, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, United Kingdom.
authors.forename: Rachel
authors.initials: R
authors.lastname: Coyle
authors.affiliation: Department of Chemistry, University of Sheffield, Sheffield S3 7HF, United Kingdom.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Baggaley
authors.affiliation: Academic Unit of Molecular Oncology, Department of Oncology, Sheffield Cancer Research Centre, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Bottomley
authors.affiliation: Department of Chemistry, University of Sheffield, Sheffield S3 7HF, United Kingdom.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Weinstein
authors.affiliation: Academic Unit of Molecular Oncology, Department of Oncology, Sheffield Cancer Research Centre, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, United Kingdom.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Bryant
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D008024:Ligands; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D010984:Platinum / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D017319:Photosensitizing Agents; D010984:Platinum