A Multi-action and Multi-target RuII-PtIV Conjugate Combining Cancer-Activated Chemotherapy and Photodynamic Therapy to Overcome Drug Resistant Cancers

Pt-II complexes are commonly used to treat cancer. 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, Ru-II polypyridine complexes have gained much attention as photosensitizers for use in photodynamic therapy due to their attractive characteristics. In this article, a novel Pt-IV-Ru-II conjugate, which combines cancer activated chemotherapy with PDT, 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 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.