A Multiaction and Multitarget Ru(II)-Pt(IV) Conjugate Combining Cancer Activated Chemotherapy and Photodynamic Therapy to Overcome Drug Resistant Cancers

International audienceCancer has emerged as one of the deadliest diseases worldwide. Pt(II) complexes are commonly used to treat this condition. To reduce their side effects and improve their pharmacological properties, Pt(IV) complexes are being developed as prodrug candidates that are activated by reduction in cancer cells. Concomitantly, photodynamic therapy (PDT) has received increasing attention over the last years. Among other compounds studied as photosensitizers (PSs), Ru(II) polypyridine complexes have gained much attention over the recent years due to their attractive characteristics. In this article, the first example of a novel Pt(IV)-Ru(II) conjugate, which combines cancer activated chemotherapy with photodynamic therapy, is presented. Upon entering the cancer cell, the Pt(IV) centre is reduced to Pt(II) and the axial ligands including the Ru(II) complex and phenylbutyrate are released. As each component has its individual target, the conjugate exerts a multitarget and multiaction effect with (photo-)cytotoxicity values upon irradiation up to clinically relevant 595 nm in the low nanomolar range in various (drug resistant) 2D monolayer cancer cells and 3D multicellular tumour spheroids