A Multi‐action and Multi‐target Ru<sup>II</sup>–Pt<sup>IV</sup> Conjugate Combining Cancer‐Activated Chemotherapy and Photodynamic Therapy to Overcome Drug Resistant Cancers
Johannes Karges, Thirumal Yempala, Mickaël Tharaud, Dan Gibson, Gilles Gasser
Abstract
Abstract 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.