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.check.date2017-11-11
dc.check.infoAccess to this article is restricted until 12 months after publication by request of the publisher.
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dc.contributor.authorEvans, James C.
dc.contributor.authorMalhotra, Meenakshi
dc.contributor.authorFitzgerald, Kathleen A.
dc.contributor.authorGuo, Jianfeng
dc.contributor.authorCronin, Michael F.
dc.contributor.authorO'Brien, Fergal J.
dc.contributor.authorCurtin, Caroline M.
dc.contributor.authorDarcy, Raphael
dc.contributor.authorO'Driscoll, Caitríona M.
dc.contributor.funderIrish Cancer Societyen
dc.contributor.funderFP7 Ideas: European Research Councilen
dc.date.accessioned2017-07-31T11:23:56Z
dc.date.available2017-07-31T11:23:56Z
dc.date.issued2016-11-11
dc.date.updated2017-07-31T10:56:25Z
dc.description.abstractIn 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, pen
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationEvans, 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.6b00646en
dc.identifier.doi10.1021/acs.molpharmaceut.6b00646
dc.identifier.endpage52en
dc.identifier.issn1543-8384
dc.identifier.issued1en
dc.identifier.journaltitleMolecular Pharmaceuticsen
dc.identifier.startpage42en
dc.identifier.urihttps://hdl.handle.net/10468/4411
dc.identifier.volume14en
dc.language.isoenen
dc.publisherACS Publicationsen
dc.relation.projectinfo:eu-repo/grantAgreement/EC/FP7::SP2::ERC/239685/EU/Collagen scaffolds for bone regeneration: applied biomaterials, bioreactor and stem cell technology/COLLREGENen
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.6b00646en
dc.subjectBone microenvironmenten
dc.subjectCollagen scaffoldsen
dc.subjectProstate cancer metastasisen
dc.subjectRNAien
dc.subjectSigma receptoren
dc.subjectsiRNA deliveryen
dc.titleFormulation and evaluation of anisamide-targeted amphiphilic cyclodextrin nanoparticles to promote therapeutic gene silencing in a 3D prostate cancer bone metastases modelen
dc.typeArticle (peer-reviewed)en
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