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.authorLuan, Xue
dc.contributor.authorRahme, Kamil
dc.contributor.authorCong, Zhongcheng
dc.contributor.authorWang, Limei
dc.contributor.authorZou, Yifang
dc.contributor.authorHe, Yan
dc.contributor.authorYang, Hao
dc.contributor.authorHolmes, Justin D.
dc.contributor.authorO'Driscoll, Caitríona M.
dc.contributor.authorGuo, Jianfeng
dc.contributor.funderDepartment of Science and Technology of Jilin Provinceen
dc.contributor.funderJilin Universityen
dc.date.accessioned2019-03-04T15:21:00Z
dc.date.available2019-03-04T15:21:00Z
dc.date.issued2019-02-16
dc.date.updated2019-03-01T14:19:35Z
dc.description.abstractSmall 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.sponsorshipDepartment 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.description.statusPeer revieweden
dc.description.versionSubmitted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationLuan, 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.2019.02.013en
dc.identifier.doi10.1016/j.ejpb.2019.02.013
dc.identifier.endpage67en
dc.identifier.issn0939-6411
dc.identifier.journaltitleEuropean Journal of Pharmaceutics and Biopharmaceuticsen
dc.identifier.startpage56en
dc.identifier.urihttps://hdl.handle.net/10468/7562
dc.identifier.volume137en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.urihttps://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 licenseen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectNon-viral siRNA deliveryen
dc.subjectCancer gene therapyen
dc.subjectCombination therapyen
dc.subjectProstate canceren
dc.titleAnisamide-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 miceen
dc.typeArticle (peer-reviewed)en
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