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Type: Journal article
Title: Synthesis and biological evaluation of a class of mitochondrially-targeted gadolinium(III) agents
Author: Morrison, D.
Aitken, J.
de Jonge, M.
Issa, F.
Harris, H.
Rendina, L.
Citation: Chemistry A European Journal, 2014; 20(50):16602-16612
Publisher: ChemPubSoc Europe
Issue Date: 2014
ISSN: 0947-6539
Statement of
Daniel E. Morrison, Jade B. Aitken, Martin D. de Jonge, Fatiah Issa, Hugh H. Harris, and Louis M. Rendina
Abstract: A structure-activity relationship study of a library of novel bifunctional Gd(III) complexes covalently linked to arylphosphonium cations is reported. Such complexes have been designed for potential application in binary cancer therapies such as neutron capture therapy and photon activation therapy. A positive correlation was found between lipophilicity and cytotoxicity of the complexes. Mitochondria uptake was determined by means of inductively coupled plasma mass spectrometry (ICP-MS), and Gd uptake was determined by means of quantification using synchrotron X-ray fluorescence (XRF) imaging. A negative correlation between lipophilicity and tumour selectivity of the Gd(III) complexes was demonstrated. This study highlights the delicate balance required to minimise in vitro cytotoxicity and optimise in vitro tumour selectivity and mitochondrial localisation for this new class of mitochondrially-targeted binary therapy agents. We also report the highest in vitro tumour selectivity for any Gd agent reported to date, with a T/N (tumour/normal cell) ratio of up to 23.5±6.6.
Keywords: X-ray fluorescence; gadolinium; mitochondria; phosphonium; tumours
Rights: © 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
RMID: 0030018744
DOI: 10.1002/chem.201404107
Appears in Collections:Medicine publications

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