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.contributor.author Luan, Xue
dc.contributor.author Rahme, Kamil
dc.contributor.author Cong, Zhongcheng
dc.contributor.author Wang, Limei
dc.contributor.author Zou, Yifang
dc.contributor.author He, Yan
dc.contributor.author Yang, Hao
dc.contributor.author Holmes, Justin D.
dc.contributor.author O'Driscoll, Caitríona M.
dc.contributor.author Guo, Jianfeng
dc.date.accessioned 2019-03-04T15:21:00Z
dc.date.available 2019-03-04T15:21:00Z
dc.date.issued 2019-02-16
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 en
dc.identifier.startpage 56 en
dc.identifier.endpage 67 en
dc.identifier.issn 0939-6411
dc.identifier.uri http://hdl.handle.net/10468/7562
dc.identifier.doi 10.1016/j.ejpb.2019.02.013
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. en
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) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Elsevier en
dc.relation.uri https://www.sciencedirect.com/science/article/pii/S093964111831186X
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 en
dc.subject Cancer gene therapy en
dc.subject Combination therapy en
dc.subject Prostate cancer en
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 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 2019-03-01T14:19:35Z
dc.description.version Submitted Version en
dc.internal.rssid 475884521
dc.contributor.funder Department of Science and Technology of Jilin Province en
dc.contributor.funder Jilin University en
dc.description.status Peer reviewed en
dc.identifier.journaltitle European Journal of Pharmaceutics and Biopharmaceutics en
dc.internal.copyrightchecked No !!CORA!! en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress j.holmes@ucc.ie en


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© 2018 Published by Elsevier B.V. This submitted manuscript version is made available under the CC-BY-NC-ND 4.0 license Except where otherwise noted, this item's license is described as © 2018 Published by Elsevier B.V. This submitted manuscript version is made available under the CC-BY-NC-ND 4.0 license
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