Novel Ru(ii) complexes with multiple anticancer photoreactivity: ligand exchange, photoredox catalysis, reactive oxygen generation and endoperoxide formation

The hypoxic microenvironment and drug resistance of cancer cells have become a huge threat for clinical anticancer therapy. Anticancer phototherapy providing spatial and temporal control over drug activation may conquer this problem. Herein, we report a novel photoactivated Ru(II) complex (Ru2) with multiple activities including photochemotherapy, photodynamic and photocatalytic therapy, and endoperoxide formation. Upon white light irradiation, Ru2 can dissociate the coordinating ligands and form endoperoxides, produce diverse reactive oxygen species and catalytically oxidize cellular coenzymes. As a result, Ru2 shows promising antiproliferation activity toward cisplatin and 5-fluorouracil resistant tumor cell lines under normoxia and hypoxia. The multifunctional design strategy of metal-based anticancer drugs offers novel efficient therapeutics to combat drug-resistant cancer cells under hypoxia.