A Multi-action and Multi-target Ru -Pt Conjugate Combining Cancer-Activated Chemotherapy and Photodynamic Therapy to Overcome Drug Resistant Cancers.

Pt complexes are commonly used to treat cancer. To reduce their side effects and improve their pharmacological properties, Pt complexes are being developed as prodrug candidates that are activated by reduction in cancer cells. Concomitantly, Ru polypyridine complexes have gained much attention as photosensitizers for use in photodynamic therapy due to their attractive characteristics. In this article, a novel Pt -Ru conjugate, which combines cancer activated chemotherapy with PDT, is presented. Upon entering the cancer cell, the Pt centre is reduced to Pt and the axial ligands including the Ru complex and phenylbutyrate are released. As each component has its individual targets, the conjugate exerts a multi-target and multi-action effect with (photo-)cytotoxicity values upon irradiation up to 595 nm in the low nanomolar range in various (drug resistant) 2D monolayer cancer cells and 3D multicellular tumour spheroids.