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

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dc.contributor.authorGuo, Jianfeng
dc.contributor.authorO'Driscoll, Caitríona M.
dc.contributor.authorHolmes, Justin D.
dc.contributor.authorRahme, Kamil
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderIrish Research Councilen
dc.date.accessioned2018-01-26T15:49:12Z
dc.date.available2018-01-26T15:49:12Z
dc.date.issued2016-05-14
dc.date.updated2018-01-26T13:00:35Z
dc.description.abstractThe 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.sponsorshipIrish Research Council (Government of Ireland Postdoctoral Fellowship (GOIPD/2013/150))en
dc.description.statusPeer revieweden
dc.description.versionSubmitted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationGuo, 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.2016.05.027en
dc.identifier.doi10.1016/j.ijpharm.2016.05.027
dc.identifier.endpage27en
dc.identifier.issn0378-5173
dc.identifier.issued1-2en
dc.identifier.journaltitleInternational Journal of Pharmaceuticsen
dc.identifier.startpage16en
dc.identifier.urihttps://hdl.handle.net/10468/5335
dc.identifier.volume509en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2278/IE/Advanced Materials and BioEngineering Research Centre (AMBER)/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.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectGold nanoparticlesen
dc.subjectTargeting ligandsen
dc.subjectReceptor-mediated internalisationen
dc.subjectNon-viral siRNA deliveryen
dc.subjectProstate cancer gene therapyen
dc.titleBioconjugated gold nanoparticles enhance cellular uptake: a proof of concept study for siRNA delivery in prostate cancer cellsen
dc.typeArticle (peer-reviewed)en
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