Self-assembled cationic β-cyclodextrin nanostructures for siRNA delivery
Singh, Raghvendra Pratap; Hidalgo, Tania; Cazade, Pierre-Andre; Darcy, Raphael; Cronin, Michael F.; Dorin, Irina; O'Driscoll, Caitríona M.; Thompson, Damien
Date:
2019-02-05
Copyright:
© 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.8b01307
Full text restriction information:
Access to this article is restricted until 12 months after publication by request of the publisher.
Restriction lift date:
2020-02-05
Citation:
Singh, 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.8b01307
Abstract:
Functionalised 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.
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