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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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Supplementary files

Article information


Submitted
31 May 2011
Accepted
12 Jul 2011
First published
11 Aug 2011

Chem. Sci., 2011,2, 2135-2142
Article type
Edge Article

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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