N-heterocyclic carbene-iridium complexes as photosensitizers for in vitro photodynamic therapy to trigger non-apoptotic cell death in cancer cells
Résumé
A series of seven novel iridium complexes was synthetized and characterized as potential photosensitizers for photodynamic therapy (PDT) applications. Among them, four complexes were evaluated in vitro for their anti-proliferative activity with and without irradiation on a panel of five tumor cell lines namely PC-3 (prostate cancer), T24 (bladder cancer), MCF7 (breast cancer), A549 (lung cancer) and HeLa (cervix cancer) and two non-tumor cell models (NIH-3T3 fibroblasts and MC3T3 osteoblasts). After irradiation at 458 nm, all tested complexes showed a strong selectivity against tumor cells with selectivity index ranging from 8 to 34 compared to non-tumor cells. The cytotoxic effect of all these complexes was found to be independent of the anti-apoptotic protein Bcl-xL. The compound exhibiting the best selectivity, complex 4a, was selected for further investigations. Complex 4a was mainly localized in mitochondria. We found that the loss of cell viability, decrease in ATP and GSH content induced by complex 4a were independent of both Bcl-xL and caspase activation, supporting a non-apoptotic cell death.
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