Formulation and evaluation of anisamide-targeted amphiphilic cyclodextrin nanoparticles to promote therapeutic gene silencing in a 3D prostate cancer bone metastases model

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dc.contributor.author Evans, James C.
dc.contributor.author Malhotra, Meenakshi
dc.contributor.author Fitzgerald, Kathleen A.
dc.contributor.author Guo, Jianfeng
dc.contributor.author Cronin, Michael F.
dc.contributor.author O'Brien, Fergal J.
dc.contributor.author Curtin, Caroline M.
dc.contributor.author Darcy, Raphael
dc.contributor.author O'Driscoll, Caitríona M.
dc.date.accessioned 2017-07-31T11:23:56Z
dc.date.available 2017-07-31T11:23:56Z
dc.date.issued 2016-11-11
dc.identifier.citation Evans, J. C., Malhotra, M., Fitzgerald, K. A., Guo, J., Cronin, M. F., Curtin, C. M., O’Brien, F. J., Darcy, R. and O’Driscoll, C. M. (2016) 'Formulation and evaluation of anisamide-targeted amphiphilic cyclodextrin nanoparticles to promote therapeutic gene silencing in a 3D prostate cancer bone metastases model', Molecular Pharmaceutics, 14(1), pp. 42-52. doi:10.1021/acs.molpharmaceut.6b00646 en
dc.identifier.volume 14 en
dc.identifier.issued 1 en
dc.identifier.startpage 42 en
dc.identifier.endpage 52 en
dc.identifier.issn 1543-8384
dc.identifier.uri http://hdl.handle.net/10468/4411
dc.identifier.doi 10.1021/acs.molpharmaceut.6b00646
dc.description.abstract In recent years, RNA interference (RNAi) has emerged as a potential therapeutic offering the opportunity to treat a wide range of diseases, including prostate cancer. Modified cyclodextrins have emerged as effective gene delivery vectors in a range of disease models. The main objective of the current study was to formulate anisamide-targeted cyclodextrin nanoparticles to interact with the sigma receptor (overexpressed on the surface of prostate cancer cells). The inclusion of octaarginine in the nanoparticle optimized uptake and endosomal release of siRNA in two different prostate cancer cell lines (PC3 and DU145 cells). Resulting nanoparticles were less than 200 nm in size with a cationic surface charge (∼+20 mV). In sigma receptor-positive cell lines, the uptake of anisamide-targeted nanoparticles was reduced in the presence of the sigma receptor competitive ligand, haloperidol. When cells were transfected in 2D, the levels of PLK1 mRNA knockdown elicited by targeted versus untargeted nanoparticles tended to be greater but the differences were not statistically different. In contrast, when cells were grown on 3D scaffolds, recapitulating bone metastasis, targeted formulations showed significantly higher levels of PLK1 mRNA knockdown (46% for PC3 and 37% for DU145, p en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher ACS Publications en
dc.rights © 2016, American Chemical Society. This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.6b00646 en
dc.subject Bone microenvironment en
dc.subject Collagen scaffolds en
dc.subject Prostate cancer metastasis en
dc.subject RNAi en
dc.subject Sigma receptor en
dc.subject siRNA delivery en
dc.title Formulation and evaluation of anisamide-targeted amphiphilic cyclodextrin nanoparticles to promote therapeutic gene silencing in a 3D prostate cancer bone metastases model 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.
dc.check.info
dc.check.date 2017-11-11
dc.date.updated 2017-07-31T10:56:25Z
dc.description.version Accepted Version en
dc.internal.rssid 405049673
dc.contributor.funder Irish Cancer Society en
dc.contributor.funder FP7 Ideas: European Research Council en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Molecular Pharmaceutics en
dc.internal.copyrightchecked Yes en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress caitriona.odriscoll@ucc.ie en
dc.relation.project info:eu-repo/grantAgreement/EC/FP7::SP2::ERC/239685/EU/Collagen scaffolds for bone regeneration: applied biomaterials, bioreactor and stem cell technology/COLLREGEN en


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