Folate-targeted amphiphilic cyclodextrin nanoparticles incorporating a fusogenic peptide deliver therapeutic siRNA and inhibit the invasive capacity of 3D prostate cancer tumours

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dc.contributor.author Evans, James C.
dc.contributor.author Malhotra, Meenakshi
dc.contributor.author Sweeney, Katrina
dc.contributor.author Darcy, Raphael
dc.contributor.author Nelson, Colleen C.
dc.contributor.author Hollier, Brett G.
dc.contributor.author O'Driscoll, Caitríona M.
dc.date.accessioned 2017-10-05T10:56:05Z
dc.date.available 2017-10-05T10:56:05Z
dc.date.issued 2017-09-13
dc.identifier.citation Evans, J. C., Malhotra, M., Sweeney, K., Darcy, R., Nelson, C. C., Hollier, B. G. and O’Driscoll, C. M. (2017) 'Folate-targeted amphiphilic cyclodextrin nanoparticles incorporating a fusogenic peptide deliver therapeutic siRNA and inhibit the invasive capacity of 3D prostate cancer tumours', International Journal of Pharmaceutics, 532(1), pp. 511-518. doi: 10.1016/j.ijpharm.2017.09.013 en
dc.identifier.volume 532 en
dc.identifier.issued 1 en
dc.identifier.startpage 511 en
dc.identifier.endpage 518 en
dc.identifier.issn 0378-5173
dc.identifier.uri http://hdl.handle.net/10468/4836
dc.identifier.doi 10.1016/j.ijpharm.2017.09.013
dc.description.abstract The main barrier to the development of an effective RNA interference (RNAi) therapy is the lack of a suitable delivery vector. Modified cyclodextrins have emerged in recent years for the delivery of siRNA. In the present study, a folate-targeted amphiphilic cyclodextrin was formulated using DSPE-PEG5000-folate to target prostate cancer cells. The fusogenic peptide GALA was included in the formulation to aid in the endosomal release of siRNA. Targeted nanoparticles were less than 200 nm in size with a neutral surface charge. The complexes were able to bind siRNA and protect it from serum nucleases. Incubation with excess free folate resulted in a significant decrease in the uptake of targeted nanoparticles in LNCaP and PC3 cells, both of which have been reported to have differing pathways of folate uptake. There was a significant reduction in the therapeutic targets, ZEB1 and NRP1 at mRNA and protein level following treatment with targeted complexes. In preliminary functional assays using 3D spheroids, treatment of PC3 tumours with targeted complexes with ZEB1 and NRP1 siRNA resulted in more compact colonies relative to the untargeted controls and inhibited infiltration into the Matrigel™ layer. en
dc.description.sponsorship Irish Cancer Society ((CRS12EVA), (PCI11ODR)); Irish Research Council (GOIPD/2014/151); National Health and Medical Research Council (NHMRC (APP1100417)); Cure Cancer Australia Foundation(PdCCRS); Prostate Cancer Foundation of Australia and Movember Foundation (Movember Revolutionary Team Award) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Elsevier en
dc.relation.uri http://www.sciencedirect.com/science/article/pii/S0378517317308682
dc.rights © 2017 Elsevier B.V. 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 RNAi en
dc.subject Cyclodextrin en
dc.subject GALA en
dc.subject siRNA delivery en
dc.subject Prostate cancer en
dc.subject Metastasis en
dc.subject Folate en
dc.title Folate-targeted amphiphilic cyclodextrin nanoparticles incorporating a fusogenic peptide deliver therapeutic siRNA and inhibit the invasive capacity of 3D prostate cancer tumours 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 for 12 months after publication by request of the publisher. en
dc.check.date 2018-09-13
dc.date.updated 2017-10-05T10:46:47Z
dc.description.version Accepted Version en
dc.internal.rssid 413703668
dc.contributor.funder Irish Cancer Society en
dc.contributor.funder Irish Research Council en
dc.contributor.funder National Health and Medical Research Council en
dc.contributor.funder Cancer Australia en
dc.contributor.funder Prostate Cancer Foundation of Australia en
dc.contributor.funder Cure Cancer Australia Foundation en
dc.contributor.funder Department of Health, Australian Government en
dc.contributor.funder Movember Foundation en
dc.description.status Peer reviewed en
dc.identifier.journaltitle International Journal of Pharmaceutics 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. 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. This manuscript version is made available under the CC BY-NC-ND 4.0 license.
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