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Issue 11, 2011
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Visualising the hypoxia selectivity of cobalt(III) prodrugs

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Abstract

Hypoxic cancer cells have a more aggressive phenotype than cells in a normoxic environment and are often refractory to current chemotherapy protocols due to an altered proliferation rate. They also represent a means of targeting cancer chemotherapy. We have developed a 3-dimensional cell culture model that readily identifies live hypoxic cells by expression of the Eos photo-convertible green fluorescent protein. Using this model, we have examined the diffusion and hypoxia selectivity of two model Co(III) based compounds. The Co(III) compounds have been designed to target hypoxic cells within a tumour and have fluorescent axial ligands. The fluorescent ligands function as model cytotoxins and their fluorescence is quenched on binding to Co(III). The ligands are released upon the reduction of Co(III) to Co(II) and the recovery of fluorescence enables the detection of the released ligands by confocal microscopy. Despite similarities in electrochemical potential and cytotoxicity, the penetration of the compounds into spheroids and uptake into hypoxic cells was found to differ depending on the properties of the released ligand.

Graphical abstract: Visualising the hypoxia selectivity of cobalt(iii) prodrugs

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Publication details

The article was received on 31 May 2011, accepted on 12 Jul 2011 and first published on 11 Aug 2011


Article type: Edge Article
DOI: 10.1039/C1SC00337B
Citation: Chem. Sci., 2011,2, 2135-2142
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    Visualising the hypoxia selectivity of cobalt(III) prodrugs

    B. J. Kim, T. W. Hambley and N. S. Bryce, Chem. Sci., 2011, 2, 2135
    DOI: 10.1039/C1SC00337B

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