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

dc.contributor.authorFitzgerald, Kathleen A.
dc.contributor.authorRahme, Kamil
dc.contributor.authorGuo, Jianfeng
dc.contributor.authorHolmes, Justin D.
dc.contributor.authorO'Driscoll, Caitríona M.
dc.contributor.funderIrish Cancer Societyen
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderIrish Research Councilen
dc.date.accessioned2018-01-17T11:49:31Z
dc.date.available2018-01-17T11:49:31Z
dc.date.issued2016-03-08
dc.date.updated2018-01-16T17:38:10Z
dc.description.abstractMetastatic 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.sponsorshipIrish Cancer Society (Project Grant PCI11ODR); Irish Research Council (Postdoctoral Fellowship)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationFitzgerald, 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/c6tb00082gen
dc.identifier.doi10.1039/c6tb00082g
dc.identifier.endpage2252en
dc.identifier.issn2050-750X
dc.identifier.issued13en
dc.identifier.journaltitleJournal of Materials Chemistry Ben
dc.identifier.startpage2242en
dc.identifier.urihttps://hdl.handle.net/10468/5286
dc.identifier.volume4en
dc.language.isoenen
dc.publisherRoyal Society of Chemistryen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2278/IE/Advanced Materials and BioEngineering Research Centre (AMBER)/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/C6TB00082Gen
dc.subjectGolden
dc.subjectNanoparticlesen
dc.subjectIn-vitro evaluationen
dc.subjectPolyethyleniminesen
dc.subjectPositively chargeden
dc.subjectProof of principlesen
dc.subjectProstate cancer cellsen
dc.subjectSerum-free mediumen
dc.subjectTargeted nanoparticleen
dc.subjectBinsen
dc.subjectBody fluidsen
dc.subjectCellsen
dc.subjectChemotherapyen
dc.subjectDiseasesen
dc.subjectEnzyme inhibitionen
dc.subjectFiber optic sensorsen
dc.subjectGold coatingsen
dc.subjectMetal nanoparticlesen
dc.subjectNanoparticlesen
dc.subjectRNAen
dc.subjectSynthesis (chemical)en
dc.subjectUrologyen
dc.titleAnisamide-targeted gold nanoparticles for siRNA delivery in prostate cancer - synthesis, physicochemical characterisation and in vitro evaluationen
dc.typeArticle (peer-reviewed)en
Files
Original bundle
Now showing 1 - 2 of 2
Loading...
Thumbnail Image
Name:
2015-12-21_COD_Amendments_1.doc
Size:
2.14 MB
Format:
Microsoft Word
Description:
Author's original
Loading...
Thumbnail Image
Name:
4668.pdf
Size:
1.02 MB
Format:
Adobe Portable Document Format
Description:
Accepted version
License bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
license.txt
Size:
2.71 KB
Format:
Item-specific license agreed upon to submission
Description: