dc.contributor.author |
Luan, Xue |
|
dc.contributor.author |
Rahme, Kamil |
|
dc.contributor.author |
Cong, Zhongcheng |
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dc.contributor.author |
Wang, Limei |
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dc.contributor.author |
Zou, Yifang |
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dc.contributor.author |
He, Yan |
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dc.contributor.author |
Yang, Hao |
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dc.contributor.author |
Holmes, Justin D. |
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dc.contributor.author |
O'Driscoll, Caitríona M. |
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dc.contributor.author |
Guo, Jianfeng |
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dc.date.accessioned |
2019-03-04T15:21:00Z |
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dc.date.available |
2019-03-04T15:21:00Z |
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dc.date.issued |
2019-02-16 |
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dc.identifier.citation |
Luan, X., Rahme, K., Cong, Z., Wang, L., Zou, Y., He, Y., Yang, H., Holmes, J. D., O'Driscoll, C. M. and Guo, J. (2019) 'Anisamide-targeted PEGylated gold nanoparticles designed to target prostate cancer mediate: Enhanced systemic exposure of siRNA, tumour growth suppression and a synergistic therapeutic response in combination with paclitaxel in mice', European Journal of Pharmaceutics and Biopharmaceutics, 137, pp. 56-67. doi: 10.1016/j.ejpb.2019.02.013 |
en |
dc.identifier.volume |
137 |
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dc.identifier.startpage |
56 |
en |
dc.identifier.endpage |
67 |
en |
dc.identifier.issn |
0939-6411 |
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dc.identifier.uri |
http://hdl.handle.net/10468/7562 |
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dc.identifier.doi |
10.1016/j.ejpb.2019.02.013 |
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dc.description.abstract |
Small interfering RNA (siRNA) has recently illustrated therapeutic potential for malignant disorders. However, the clinical application of siRNA-based therapeutics is significantly retarded by the paucity of successful delivery systems. Recently, multifunctional gold nanoparticles (AuNPs) as non-viral delivery carriers have shown promise for transporting chemotherapeutics, proteins/peptides, and genes. In this study, AuNPs capped with polyethylenimine (PEI) and PEGylated anisamide (a ligand known to target the sigma receptor) have been developed to produce a range of positively charged anisamide-targeted PEGylated AuNPs (namely Au-PEI-PEG-AA). The anisamide-targeted AuNPs effectively complexed siRNA via electrostatic interaction, and the resultant complex (Au110-PEI-PEG5000-AA.siRNA) illustrated favourable physicochemical characteristics, including particle size, surface charge, and stability. In vitro, anisamide-targeted AuNPs selectively bound to human prostate cancer PC-3 cells, inducing efficient endosomal escape of siRNA, and effective downregulation of the RelA gene. In vivo, prolonged systemic exposure of siRNA was achieved by anisamide-targeted AuNPs resulting in significant tumour growth suppression in a PC3 xenograft mouse model without an increase in toxicity. In addition, a combination of siRNA-mediated NF-κB knockdown using anisamide-targeted AuNPs with Paclitaxel produced a synergistic therapeutic response, thus providing a promising therapeutic strategy for the treatment of prostate cancer. |
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dc.description.sponsorship |
Department of Science and Technology of Jilin Province (Outstanding Youth Foundation from the Department of Science and Technology, Jilin Province, China (20170520046JH)); Jilin University (the Start-Up Research Grant Program from Jilin University (451170301168, 451160102052, 419080500667); the Fundamental Research Funds for the Central Universities, China) |
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dc.format.mimetype |
application/pdf |
en |
dc.language.iso |
en |
en |
dc.publisher |
Elsevier |
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dc.relation.uri |
https://www.sciencedirect.com/science/article/pii/S093964111831186X |
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dc.rights |
© 2018 Published by Elsevier B.V. This submitted manuscript version is made available under the CC-BY-NC-ND 4.0 license |
en |
dc.rights.uri |
http://creativecommons.org/licenses/by-nc-nd/4.0/ |
en |
dc.subject |
Non-viral siRNA delivery |
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dc.subject |
Cancer gene therapy |
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dc.subject |
Combination therapy |
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dc.subject |
Prostate cancer |
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dc.title |
Anisamide-targeted PEGylated gold nanoparticles designed to target prostate cancer mediate: enhanced systemic exposure of siRNA, tumour growth suppression and a synergistic therapeutic response in combination with paclitaxel in mice |
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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 |
en |
dc.date.updated |
2019-03-01T14:19:35Z |
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dc.description.version |
Submitted Version |
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dc.internal.rssid |
475884521 |
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dc.contributor.funder |
Department of Science and Technology of Jilin Province
|
en |
dc.contributor.funder |
Jilin University
|
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dc.description.status |
Peer reviewed |
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dc.identifier.journaltitle |
European Journal of Pharmaceutics and Biopharmaceutics |
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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 |
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