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

Johannes Karges, Thirumal Yempala, Mickaël Tharaud, Dan Gibson*, Gilles Gasser

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

183 Scopus citations

Abstract

PtII complexes are commonly used to treat cancer. To reduce their side effects and improve their pharmacological properties, PtIV complexes are being developed as prodrug candidates that are activated by reduction in cancer cells. Concomitantly, RuII polypyridine complexes have gained much attention as photosensitizers for use in photodynamic therapy due to their attractive characteristics. In this article, a novel PtIV–RuII conjugate, which combines cancer activated chemotherapy with PDT, is presented. Upon entering the cancer cell, the PtIV centre is reduced to PtII and the axial ligands including the RuII 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.

Original languageEnglish
Pages (from-to)7069-7075
Number of pages7
JournalAngewandte Chemie - International Edition
Volume59
Issue number18
DOIs
StatePublished - 27 Apr 2020

Bibliographical note

Publisher Copyright:
© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

  • bioinorganic chemistry
  • metals in medicine
  • photodynamic therapy
  • platinum prodrugs

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