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

doi:10.1002/anie.201916400

A Multi-action and Multi-target Ru^II–Pt^IV 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

School of Pharmacy

Research output: Contribution to journal › Article › peer-review

211 Scopus citations

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.

Original language	English
Pages (from-to)	7069-7075
Number of pages	7
Journal	Angewandte Chemie - International Edition
Volume	59
Issue number	18
DOIs	https://doi.org/10.1002/anie.201916400
State	Published - 27 Apr 2020

Bibliographical note

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

bioinorganic chemistry
metals in medicine
photodynamic therapy
platinum prodrugs

Access to Document

10.1002/anie.201916400

Cite this

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

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.",

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A Multi-action and Multi-target Ru^II–Pt^IV Conjugate Combining Cancer-Activated Chemotherapy and Photodynamic Therapy to Overcome Drug Resistant Cancers. / Karges, Johannes; Yempala, Thirumal; Tharaud, Mickaël et al.
In: Angewandte Chemie - International Edition, Vol. 59, No. 18, 27.04.2020, p. 7069-7075.

Research output: Contribution to journal › Article › peer-review

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AU - Karges, Johannes

AU - Yempala, Thirumal

AU - Tharaud, Mickaël

AU - Gibson, Dan

AU - Gasser, Gilles

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AB - 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.

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