Anisamide-targeted gold nanoparticles for siRNA delivery in prostate cancer - synthesis, physicochemical characterisation and in vitro evaluation

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dc.contributor.author Fitzgerald, Kathleen A.
dc.contributor.author Rahme, Kamil
dc.contributor.author Guo, Jianfeng
dc.contributor.author Holmes, Justin D.
dc.contributor.author O'Driscoll, Caitríona M.
dc.date.accessioned 2018-01-17T11:49:31Z
dc.date.available 2018-01-17T11:49:31Z
dc.date.issued 2016-03-08
dc.identifier.citation Fitzgerald, K. A., Rahme, K., Guo, J., Holmes, J. D. and O'Driscoll, C. M. (2016) 'Anisamide-targeted gold nanoparticles for siRNA delivery in prostate cancer - synthesis, physicochemical characterisation and in vitro evaluation', Journal of Materials Chemistry B, 4(13), pp. 2242-2252. doi: 10.1039/c6tb00082g en
dc.identifier.volume 4 en
dc.identifier.issued 13 en
dc.identifier.startpage 2242 en
dc.identifier.endpage 2252 en
dc.identifier.issn 2050-750X
dc.identifier.uri http://hdl.handle.net/10468/5286
dc.identifier.doi 10.1039/c6tb00082g
dc.description.abstract Metastatic prostate cancer is a leading cause of cancer-related death in men and current chemotherapies are largely inadequate in terms of efficacy and toxicity. Hence improved treatments are required. The application of siRNA as a cancer therapeutic holds great promise. However, translation of siRNA into the clinic is dependent on the availability of an effective delivery system. Gold nanoparticles (AuNPs) are known to be effective and non-toxic siRNA delivery agents. In this study, a stable gold nanosphere coated with poly(ethylenimine) (PEI) was prepared to yield PEI capped AuNPs (Au-PEI). The PEI was further conjugated with the targeting ligand anisamide (AA, is known to bind to the sigma receptor overexpressed on the surface of prostate cancer cells) to produce an anisamide-targeted nanoparticle (Au-PEI-AA). The resulting untargeted and targeted nanoparticles (Au-PEI and Au-PEI-AA respectively) were positively charged and efficiently complexed siRNA. Au-PEI-AA mediated siRNA uptake into PC3 prostate cancer cells via binding to the sigma receptor. In addition, the Au-PEI-AA·siRNA complexes resulted in highly efficient knockdown of the RelA gene (∼70%) when cells were transfected in serum-free medium. In contrast, no knockdown was observed in the presence of serum, suggesting that adsorption of serum proteins inhibits the binding of the anisamide moiety to the sigma receptor. This study provides (for the first time) proof of principle that anisamide-labelled gold nanoparticles can target the sigma receptor. Further optimisation of the formulation to increase serum stability will enhance its potential to treat prostate cancer. en
dc.description.sponsorship Irish Cancer Society (Project Grant PCI11ODR); Irish Research Council (Postdoctoral Fellowship) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Royal Society of Chemistry en
dc.rights © The Royal Society of Chemistry 2016. This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Materials Chemistry B. To access the final edited and published work see http://dx.doi.org/10.1039/C6TB00082G en
dc.subject Gold en
dc.subject Nanoparticles en
dc.subject In-vitro evaluation en
dc.subject Polyethylenimines en
dc.subject Positively charged en
dc.subject Proof of principles en
dc.subject Prostate cancer cells en
dc.subject Serum-free medium en
dc.subject Targeted nanoparticle en
dc.subject Bins en
dc.subject Body fluids en
dc.subject Cells en
dc.subject Chemotherapy en
dc.subject Diseases en
dc.subject Enzyme inhibition en
dc.subject Fiber optic sensors en
dc.subject Gold coatings en
dc.subject Metal nanoparticles en
dc.subject Nanoparticles en
dc.subject RNA en
dc.subject Synthesis (chemical) en
dc.subject Urology en
dc.title Anisamide-targeted gold nanoparticles for siRNA delivery in prostate cancer - synthesis, physicochemical characterisation and in vitro evaluation 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 2018-01-16T17:38:10Z
dc.description.version Accepted Version en
dc.internal.rssid 400723614
dc.contributor.funder Irish Cancer Society en
dc.contributor.funder Science Foundation Ireland en
dc.contributor.funder Irish Research Council en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Journal of Materials Chemistry B 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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