Cyclodextrin-siRNA conjugates as versatile gene silencing agents

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dc.contributor.author Malhotra, Meenakshi
dc.contributor.author Gooding, Matt
dc.contributor.author Evans, James C.
dc.contributor.author O'Driscoll, Daniel
dc.contributor.author Darcy, Raphael
dc.contributor.author O'Driscoll, Caitríona M.
dc.date.accessioned 2018-01-08T15:45:55Z
dc.date.available 2018-01-08T15:45:55Z
dc.date.issued 2017-11-27
dc.identifier.citation Malhotra, M., Gooding, M., Evans, J. C., O'Driscoll, D., Darcy, R. and O'Driscoll, C. M. (2018) 'Cyclodextrin-siRNA conjugates as versatile gene silencing agents', European Journal of Pharmaceutical Sciences, 114, pp. 30-37. doi: 10.1016/j.ejps.2017.11.024 en
dc.identifier.volume 114 en
dc.identifier.startpage 30 en
dc.identifier.endpage 37 en
dc.identifier.issn 0928-0987
dc.identifier.uri http://hdl.handle.net/10468/5243
dc.identifier.doi 10.1016/j.ejps.2017.11.024
dc.description.abstract Functional siRNAs (luciferase and PLK1) have been conjugated to β-cyclodextrin and the ability of the conjugates to retain gene knockdown activity has been assessed by delivery to cancer cell lines using various formulations. Initially two formulations used complexation with polycations, namely Lipofectamine 2000 and an amphiphilic polycationic cyclodextrin. Gene knockdown results for human glioblastoma cells (U87) and prostate cancer cells (PC3, DU145) showed that conjugation to the cyclodextrin did not reduce gene silencing by the RNA. A third mode of delivery involved formation of targeted nanoparticles in which the conjugate was first complexed with adamantyl-PEG-ligands (targeting ligand RVG peptide or dianisamide) by adamantyl inclusion in the cyclodextrin cavities of the conjugates, followed by charge neutralisation with the cationic polymer chitosan. Enhanced knockdown was achieved by these ligand-targeted formulations. In summary, while this study illustrated the gene silencing efficacy of a simple cyclodextrin-siRNA conjugate it is envisaged that future studies will explore the use of conjugates with a modified cyclodextrin which would be self-delivering. Detailed data such as stability, lysosomal escape etc. will then be reported for each conjugate, since this will be appropriate for conjugates which are intended to exploit, rather than merely demonstrate, the concept. The present paper was intended to demonstrate the viability and generality of this novel concept. en
dc.description.sponsorship Irish Research Council (GOIPD/2014/151); Fonds de Recherche en Santé du Québec (Postdoctoral fellowship); Irish Cancer Society (CRS12EVA) 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/S092809871730653X
dc.rights © 2017 Elsevier B.V. All rights reserved. This 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 SiRNA conjugate en
dc.subject Cyclodextrins en
dc.subject Gene delivery en
dc.subject Nanoparticles en
dc.subject Prostate cancer en
dc.subject Glioblastoma en
dc.title Cyclodextrin-siRNA conjugates as versatile gene silencing agents en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Caitriona O'Driscoll, School Of Pharmacy, University College Cork, Cork, Ireland. +353-21-490-3000 Email: caitriona.odriscoll@ucc.ie en
dc.internal.availability Full text available en
dc.check.info Access to this article is restricted until 12 months after publication by request of the publisher. en
dc.check.date 2018-11-27
dc.date.updated 2018-01-08T15:38:50Z
dc.description.version Accepted Version en
dc.internal.rssid 420988429
dc.contributor.funder Irish Research Council en
dc.contributor.funder Fonds de Recherche du Québec - Santé en
dc.contributor.funder Irish Cancer Society en
dc.description.status Peer reviewed en
dc.identifier.journaltitle European Journal of Pharmaceutical Sciences en
dc.internal.copyrightchecked No !!CORA!! en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress caitriona.odriscoll@ucc.ie en


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© 2017 Elsevier B.V. All rights reserved. This 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 © 2017 Elsevier B.V. All rights reserved. This manuscript version is made available under the CC BY-NC-ND 4.0 license.
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