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. |
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dc.date.accessioned |
2018-01-17T11:49:31Z |
|
dc.date.available |
2018-01-17T11:49:31Z |
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dc.date.issued |
2016-03-08 |
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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 |
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dc.identifier.endpage |
2252 |
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dc.identifier.issn |
2050-750X |
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dc.identifier.uri |
http://hdl.handle.net/10468/5286 |
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dc.identifier.doi |
10.1039/c6tb00082g |
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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. |
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dc.description.sponsorship |
Irish Cancer Society (Project Grant PCI11ODR); Irish Research Council (Postdoctoral Fellowship) |
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dc.format.mimetype |
application/pdf |
en |
dc.language.iso |
en |
en |
dc.publisher |
Royal Society of Chemistry |
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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 |
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dc.subject |
Gold |
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dc.subject |
Nanoparticles |
en |
dc.subject |
In-vitro evaluation |
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dc.subject |
Polyethylenimines |
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dc.subject |
Positively charged |
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dc.subject |
Proof of principles |
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dc.subject |
Prostate cancer cells |
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dc.subject |
Serum-free medium |
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dc.subject |
Targeted nanoparticle |
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dc.subject |
Bins |
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dc.subject |
Body fluids |
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dc.subject |
Cells |
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dc.subject |
Chemotherapy |
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dc.subject |
Diseases |
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dc.subject |
Enzyme inhibition |
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dc.subject |
Fiber optic sensors |
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dc.subject |
Gold coatings |
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dc.subject |
Metal nanoparticles |
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dc.subject |
Nanoparticles |
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dc.subject |
RNA |
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dc.subject |
Synthesis (chemical) |
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dc.subject |
Urology |
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dc.title |
Anisamide-targeted gold nanoparticles for siRNA delivery in prostate cancer - synthesis, physicochemical characterisation and in vitro evaluation |
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dc.type |
Article (peer-reviewed) |
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dc.internal.authorcontactother |
Justin D. Holmes, Chemistry, University College Cork, Cork, Ireland. +353-21-490-3000 Email: j.holmes@ucc.ie |
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dc.internal.availability |
Full text available |
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dc.date.updated |
2018-01-16T17:38:10Z |
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dc.description.version |
Accepted Version |
en |
dc.internal.rssid |
400723614 |
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dc.contributor.funder |
Irish Cancer Society
|
en |
dc.contributor.funder |
Science Foundation Ireland
|
en |
dc.contributor.funder |
Irish Research Council
|
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dc.description.status |
Peer reviewed |
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dc.identifier.journaltitle |
Journal of Materials Chemistry B |
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dc.internal.copyrightchecked |
No !!CORA!! |
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dc.internal.licenseacceptance |
Yes |
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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 |