Metal Complexes for Two-Photon Photodynamic Therapy: A Cyclometallated Iridium Complex Induces Two-Photon Photosensitization of Cancer Cells under Near-IR Light.
Luke K McKenzieIgor V SazanovichElizabeth BaggaleyMickaële BonneauVéronique GuerchaisJ A Gareth WilliamsJulia A WeinsteinHelen E BryantPublished in: Chemistry (Weinheim an der Bergstrasse, Germany) (2016)
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.
Keyphrases
- photodynamic therapy
- cell death
- living cells
- fluorescence imaging
- cell cycle arrest
- monte carlo
- fluorescent probe
- induced apoptosis
- transition metal
- papillary thyroid
- mass spectrometry
- single molecule
- energy transfer
- high resolution
- young adults
- current status
- climate change
- radiation induced
- endoplasmic reticulum stress
- light emitting