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Nanoscale Reaction Vessels Designed for Synthesis of Copper-Drug Complexes Suitable for Preclinical Development
British Columbia Canc Res Ctr, Expt Therapeut, Vancouver, BC V5Z 1L3, Canada.;Univ British Columbia, Fac Pharmaceut Sci, Vancouver, BC, Canada..
British Columbia Canc Res Ctr, Expt Therapeut, Vancouver, BC V5Z 1L3, Canada..
British Columbia Canc Res Ctr, Expt Therapeut, Vancouver, BC V5Z 1L3, Canada..
British Columbia Canc Res Ctr, Expt Therapeut, Vancouver, BC V5Z 1L3, Canada.;Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada..
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2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 4, e0153416Article in journal (Refereed) Published
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Abstract [en]

The development of copper-drug complexes (CDCs) is hindered due to their very poor aqueous solubility. Diethyldithiocarbamate (DDC) is the primary metabolite of disulfiram, an approved drug for alcoholism that is being repurposed for cancer. The anticancer activity of DDC is dependent on complexation with copper to form copper bis-diethyldithiocarbamate (Cu(DDC)(2)), a highly insoluble complex that has not been possible to develop for indications requiring parenteral administration. We have resolved this issue by synthesizing Cu(DDC)(2) inside liposomes. DDC crosses the liposomal lipid bilayer, reacting with the entrapped copper; a reaction that can be observed through a colour change as the solution goes from a light blue to dark brown. This method is successfully applied to other CDCs including the anti-parasitic drug clioquinol, the natural product quercetin and the novel targeted agent CX-5461. Our method provides a simple, transformative solution enabling, for the first time, the development of CDCs as viable candidate anticancer drugs; drugs that would represent a brand new class of therapeutics for cancer patients.

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2016. Vol. 11, no 4, e0153416
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URN: urn:nbn:se:uu:diva-293057DOI: 10.1371/journal.pone.0153416ISI: 000373608000129PubMedID: 27055237OAI: oai:DiVA.org:uu-293057DiVA: diva2:927300
Available from: 2016-05-11 Created: 2016-05-11 Last updated: 2017-11-30Bibliographically approved

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Edwards, Katarina

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