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dc.contributor.authorWedlock, Louiseen_US
dc.contributor.authorKilburn, Matt R.en_US
dc.contributor.authorCliff, John B.en_US
dc.contributor.authorFilgueira, Luisen_US
dc.contributor.authorSaunders, Martinen_US
dc.contributor.authorBerners-Price, Sueen_US
dc.description.abstractGold(I) phosphine complexes, such as [Au(d2pype)2]Cl, (1, where d2pype is 1,2-bis(di-2-pyridyl phosphinoethane)), belong to a class of promising chemotherapeutic candidates that have been shown to be selectively toxic to tumourigenic cells, and may act via uptake into tumour cell mitochondria. For a more holistic understanding of their mechanism of action, a deeper knowledge of their subcellular distribution is required, but to date this has been limited by a lack of suitable imaging techniques. In this study the subcellular distribution of gold was visualised in situ in human breast cancer cells treated with 1, using nano-scale secondary ion mass spectrometry. NanoSIMS ion maps of 12C14N−, 31P−, 34S− and 197Au− allowed, for the first time, visualisation of cellular morphology simultaneously with subcellular distribution of gold. Energy filtered transmission electron microscopy (EFTEM) element maps for gold were also obtained, allowing for observation of nuclear and mitochondrial morphology with excellent spatial resolution, and gold element maps comparable to the data obtained with NanoSIMS. Following 2 h treatment with 1, the subcellular distribution of gold was associated with sulfur-rich regions in the nucleus and cytoplasm, supporting the growing evidence for the the mechanism of action of Au(I) compounds based on inhibition of thiol-containing protein families, such as the thioredoxin system. The combination of NanoSIMS and EFTEM has broader applicability for studying the subcellular distribution of other types of metal-based drugs.en_US
dc.publisherRoyal Society of Chemistryen_US
dc.publisher.placeUnited Kingdomen_US
dc.subject.fieldofresearchBioinorganic Chemistryen_US
dc.titleVisualizing gold inside tumour cells following treatment with an antitumour gold(I) complexen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.facultyOffice of the Snr Dep Vice Chancellor, Institute for Glycomicsen_US
gro.hasfulltextNo Full Text

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