Towards Selective Light‐Activated RuII‐Based Prodrug Candidates

Abstract

AbstractPhotoactivated chemotherapy (PACT) relies on the use of a drug and light to cause cell death. Unlike photodynamic therapy (PDT), its mechanism of action is independent of the presence of oxygen in tissues. This approach is therefore also effective for tumours characterized by hypoxic conditions. Herein we present the use of three novel RuII–polypyridyl complexes derivatized with a light‐sensitive cage and targeting peptides as selective PACT agents. Light irradiation allowed the selective release of the cytotoxic compounds from the molecular cages in living cells. Further selectivity was conferred on the system by a peptide carrier (i.e., bombesin), which targets receptors overexpressed on the membranes of HeLa cells. As expected, this peptide was found to provide an increased uptake of the systems in HeLa cells compared with normal MRC‐5 cells. As a result, for two of the compounds presented in this study, no cyto‐ or phototoxicity was observed in MRC‐5 cells, whereas in HeLa cells, upon light irradiation, IC50 values of 42.2 and 60.0 μM were obtained, which correspond to a two‐fold increase in toxicity.