4.7 Article

Photodynamic killing of cancer cells by a Platinum(II) complex with cyclometallating ligand

Journal

SCIENTIFIC REPORTS
Volume 6, Issue -, Pages -

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/srep22668

Keywords

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Funding

  1. Yorkshire Cancer Research
  2. BBSRC
  3. Wellcome Trust
  4. EPSRC KTA
  5. MRC POC funds
  6. Medical Research Council [MC_PC_12022] Funding Source: researchfish
  7. MRC [MC_PC_12022] Funding Source: UKRI

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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 mu M) 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.

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