Bioconjugated gold nanoparticles enhance cellular uptake: a proof of concept study for siRNA delivery in prostate cancer cells

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dc.contributor.author Guo, Jianfeng
dc.contributor.author O'Driscoll, Caitríona M.
dc.contributor.author Holmes, Justin D.
dc.contributor.author Rahme, Kamil
dc.date.accessioned 2018-01-26T15:49:12Z
dc.date.available 2018-01-26T15:49:12Z
dc.date.issued 2016-05-14
dc.identifier.citation Guo, J., O’Driscoll, C. M., Holmes, J. D. and Rahme, K. (2016) 'Bioconjugated gold nanoparticles enhance cellular uptake: A proof of concept study for siRNA delivery in prostate cancer cells', International Journal of Pharmaceutics, 509(1), pp. 16-27. doi: 10.1016/j.ijpharm.2016.05.027 en
dc.identifier.volume 509 en
dc.identifier.issued 1-2 en
dc.identifier.startpage 16 en
dc.identifier.endpage 27 en
dc.identifier.issn 0378-5173
dc.identifier.uri http://hdl.handle.net/10468/5335
dc.identifier.doi 10.1016/j.ijpharm.2016.05.027
dc.description.abstract The chemistry of gold nanoparticles (AuNPs) facilitates surface modifications and thus these bioengineered NPs have been investigated as a means of delivering a variety of therapeutic cargos to treat cancer. In this study we have developed AuNPs conjugated with targeting ligands to enhance cell-specific uptake in prostate cancer cells, with a purpose of providing efficient non-viral gene delivery systems in the treatment of prostate cancer. As a consequence, two novel AuNPs were synthesised namely AuNPs-PEG-Tf (negatively charged AuNPs with the transferrin targeting ligands) and AuNPs-PEI-FA (positively charged AuNPs with the folate-receptor targeting ligands). Both bioconjugated AuNPs demonstrated low cytotoxicity in prostate cancer cells. The attachment of the targeting ligand Tf to AuNPs successfully achieved receptor-mediated cellular uptake in PC-3 cells, a prostate cancer cell line highly expressing Tf receptors. The AuNPs-PEI-FA effectively complexed small interfering RNA (siRNA) through electrostatic interaction. At the cellular level the AuNPs-PEI-FA specifically delivered siRNA into LNCaP cells, a prostate cancer cell line overexpressing prostate specific membrane antigen (PSMA, exhibits a hydrolase enzymic activity with a folate substrate). Following endolysosomal escape the AuNPs-PEI-FA.siRNA formulation produced enhanced endogenous gene silencing compared to the non-targeted formulation. Our results suggest both formulations have potential as non-viral gene delivery vectors in the treatment of prostate cancer. en
dc.description.sponsorship Irish Research Council (Government of Ireland Postdoctoral Fellowship (GOIPD/2013/150)) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Elsevier en
dc.rights © 2016 Elsevier B.V. All rights reserved. This manuscript version is made available under the CC-BY-NC-ND 4.0 license. en
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/ en
dc.subject Gold nanoparticles en
dc.subject Targeting ligands en
dc.subject Receptor-mediated internalisation en
dc.subject Non-viral siRNA delivery en
dc.subject Prostate cancer gene therapy en
dc.title Bioconjugated gold nanoparticles enhance cellular uptake: a proof of concept study for siRNA delivery in prostate cancer cells en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Justin D. Holmes, Chemistry, University College Cork, Cork, Ireland. +353-21-490-3000 Email: j.holmes@ucc.ie en
dc.internal.availability Full text available en
dc.date.updated 2018-01-26T13:00:35Z
dc.description.version Submitted Version en
dc.internal.rssid 355156666
dc.contributor.funder Science Foundation Ireland en
dc.contributor.funder Irish Research Council en
dc.description.status Peer reviewed en
dc.identifier.journaltitle International Journal of Pharmaceutics en
dc.internal.copyrightchecked No !!CORA!! en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress j.holmes@ucc.ie en
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2278/IE/Advanced Materials and BioEngineering Research Centre (AMBER)/ en


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© 2016 Elsevier B.V. All rights reserved. This manuscript version is made available under the CC-BY-NC-ND 4.0 license. Except where otherwise noted, this item's license is described as © 2016 Elsevier B.V. All rights reserved. This manuscript version is made available under the CC-BY-NC-ND 4.0 license.
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