Anisamide-targeted cyclodextrin nanoparticles for siRNA delivery to prostate tumours in mice

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dc.contributor.authorGuo, Jianfeng
dc.contributor.authorOgier, Julien R.
dc.contributor.authorDesgranges, Stephane
dc.contributor.authorO'Driscoll, Caitríona M.
dc.contributor.authorDarcy, Raphael
dc.contributor.funderIrish Research Council for Science Engineering and Technologyen
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderEnterprise Irelanden
dc.date.accessioned2013-01-22T13:32:04Z
dc.date.available2013-01-22T13:32:04Z
dc.date.copyright2012
dc.date.issued2012-11
dc.date.updated2013-01-17T10:44:30Z
dc.description.abstractA hepta-guanidino-β-cyclodextrin (G-CD), its hepta-PEG conjugate (G-CD-PEG), and the corresponding anisamide-terminated PEG conjugate (G-CD-PEG-AA) have been synthesised and compared as delivery vectors for siRNA to prostate cancer cells and tumours in vivo. The G-CD-PEG-AA.siRNA formulations (in which anisamide targets the sigma receptor), but not the non-targeted formulations, induced prostate cell-specific internalisation of siRNA resulting in approximately 80% knockdown in vitro of the reporter gene, luciferase. Following intravenous administration of the anisamide-targeted formulation in a mouse prostate tumour model significant tumour inactivation with corresponding reductions in the level of vascular endothelial growth factor (VEGF) mRNA were achieved, without demonstrating enhanced toxicity. This data imply significant potential for anisamide-conjugated cyclodextrin vectors for targeted delivery of therapeutic siRNAs in the treatment of prostate cancer.en
dc.description.sponsorshipIrish Research Council for Science, Engineering and Technology (EMBARK initiative); Science Foundation Ireland (via a Strategic Research Cluster Grant (Irish Drug Delivery Network)); Enterprise Ireland (a Commercial Fund Technology Development Grant)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationGuo J., Ogier J., Desgranges S., Darcy R., and O Driscoll CM. (2012) 'Anisamide-targeted cyclodextrin nanoparticles for siRNA delivery to prostate tumours in mice'. Biomaterials, 33 (31):7775-7784. http://dx.doi.org/10.1016/j.biomaterials.2012.07.012en
dc.identifier.doi10.1016/j.biomaterials.2012.07.012
dc.identifier.endpage7784en
dc.identifier.issn0142-9612
dc.identifier.issued31en
dc.identifier.journaltitleBiomaterialsen
dc.identifier.startpage7775en
dc.identifier.urihttps://hdl.handle.net/10468/908
dc.identifier.volume33en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.urihttp://www.sciencedirect.com/science/article/pii/S0142961212007818
dc.rights© 2012, Elsevier. NOTICE: this is the author’s version of a work that was accepted for publication in Biomaterials. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Biomaterials, [33, November 2012] http://dx.doi.org/10.1016/j.biomaterials.2012.07.012en
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectCyclodextrinen
dc.subjectsiRNAen
dc.subjectNon-viral vectoren
dc.subjectPegylationen
dc.subjectAnisamideen
dc.subjectSigma receptoren
dc.subjectRNAien
dc.subjectProstate canceren
dc.subject.lcshProstate--Cancer--Treatmenten
dc.titleAnisamide-targeted cyclodextrin nanoparticles for siRNA delivery to prostate tumours in miceen
dc.typeArticle (peer-reviewed)en
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