A Multi‐action and Multi‐target RuII–PtIV Conjugate Combining Cancer‐Activated Chemotherapy and Photodynamic Therapy to Overcome Drug Resistant Cancers. Issue 18 (11th March 2020)

• Record Type: Journal Article
• Authors: Karges, Johannes; Yempala, Thirumal; Tharaud, Mickaël; Gibson, Dan; Gasser, Gilles
• Is Part Of: Angewandte Chemie international edition. Volume 59:Issue 18(2020)
• Page Start: 7069
• Page End: 7075
• Publication Date: 2020-03-11
• Subjects: bioinorganic chemistry -- metals in medicine -- photodynamic therapy -- platinum prodrugs; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201916400
• Languages: English
• ISSNs: 1433-7851

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. Abstract : Medicinal metal match : The treatment of cancer remains a major challenge in modern medicine. Herein, a novel approach combining a Pt IV complex as chemotherapeutic drug and a Ru II complex as an agent for photodynamic therapy is presented. The conjugate demonstrated to act on various cellular compartments with different mechanism on 2D monolayer cells as well as 3D multicellular tumor spheroids.