Self-assembled cationic β-cyclodextrin nanostructures for siRNA delivery

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dc.check.date2020-02-05
dc.check.infoAccess to this article is restricted until 12 months after publication by request of the publisher.en
dc.contributor.authorSingh, Raghvendra Pratap
dc.contributor.authorHidalgo, Tania
dc.contributor.authorCazade, Pierre-Andre
dc.contributor.authorDarcy, Raphael
dc.contributor.authorCronin, Michael F.
dc.contributor.authorDorin, Irina
dc.contributor.authorO'Driscoll, Caitríona M.
dc.contributor.authorThompson, Damien
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderEuropean Regional Development Funden
dc.contributor.funderEnterprise Irelanden
dc.contributor.funderHorizon 2020en
dc.date.accessioned2019-02-14T14:49:49Z
dc.date.available2019-02-14T14:49:49Z
dc.date.issued2019-02-05
dc.date.updated2019-02-14T14:37:26Z
dc.description.abstractFunctionalised cyclodextrin molecules assemble into a wide variety of superstructures in solution, which are of interest for drug delivery and other nanomaterial and biomaterial applications. Here we use a combined simulation and experimental approach to probe the co-assembly of siRNA and cationic cyclodextrin (c-CD) derivatives into a highly stable gene delivery nanostructure. The c-CD form supramolecular structures via interdigitation of their aliphatic tails, analogous to the formation of lipid bilayers and micelles. The native conformation of siRNA is preserved by the encapsulating c-CD superstructure in an extensive hydrogen bonding network between the positively charged sidearms of c-CD and the negatively charged siRNA backbone. The stability of the complexation is confirmed using isothermal titration calorimetry, and the experimental/simulation co-design methodology opens new avenues for creation of highly-engineerable gene delivery vectors.en
dc.description.sponsorshipScience Foundation Ireland (Grant Number 15/CDA/3491); Enterprise Ireland (EI innovation partnership on Advanced Biopharmaceutical Formulation)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationSingh, R. P., Hidalgo, T., Cazade, P.-A., Darcy, R., Cronin, M., Dorin, I., O'Driscoll, C. M. and Thompson, D. (2019) 'Self-assembled cationic β-cyclodextrin nanostructures for siRNA delivery', Molecular Pharmaceutics, In Press, doi: 10.1021/acs.molpharmaceut.8b01307en
dc.identifier.doi10.1021/acs.molpharmaceut.8b01307
dc.identifier.endpage18en
dc.identifier.issn1543-8384
dc.identifier.journaltitleMolecular Pharmaceuticsen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/7499
dc.language.isoenen
dc.publisherAmerican Chemical Society, ACSen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/13/RC/2073/IE/C�RAM - Centre for Research in Medical Devices/en
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Infrastructural Support/08/HEC/I1450/IE/Establishment of ICHEC as a National Facility for High-End Computing/en
dc.relation.projectinfo:eu-repo/grantAgreement/EC/H2020::MSCA-COFUND-FP/713690/EU/Career Development and Mobility Fellowships in Medical Device Research and Development: A CÚRAM Industry-Academia Training Initiative./MedTrainen
dc.relation.urihttps://pubs.acs.org/doi/10.1021/acs.molpharmaceut.8b01307
dc.rights© American Chemical Society. This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.8b01307en
dc.subjectsiRNAen
dc.subjectGene deliveryen
dc.subjectCyclodextrinen
dc.subjectSelf-assemblyen
dc.subjectMolecular dynamicsen
dc.titleSelf-assembled cationic β-cyclodextrin nanostructures for siRNA deliveryen
dc.typeArticle (peer-reviewed)en
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