Journal
CHEMISTRY-A EUROPEAN JOURNAL
Volume 23, Issue 2, Pages 234-238Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.201604792
Keywords
cancer therapy; iridium; singlet oxygen; transition metals; two-photon photodynamic therapy
Categories
Funding
- Yorkshire Cancer Research
- Cancer Research UK
- BBSRC
- EPSRC KTA
- MRC POC funds
- University of Durham
- CNRS (France)
- Welcome Trust [WT093134AIA]
- MRC SHIMA [MR/K015753/1]
- MRC [MR/K015753/1, MC_PC_12022] Funding Source: UKRI
- Medical Research Council [MC_PC_12022] Funding Source: researchfish
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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 Jcm(-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.
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