Peer-Reviewed Journal Details
Mandatory Fields
Singh, Raghvendra Pratap; Hidalgo, Tania; Cazade, Pierre-Andre; Darcy, Raphael; Cronin, Michael; Dorin, Irina; O'Driscoll, Caitriona M.; Thompson, Damien
2019
Unknown
Molecular Pharmaceutics
Self-assembled cationic -cyclodextrin nanostructures for siRNA delivery
In Press
WOS: 28 ()
Optional Fields
siRNA Gene delivery Cyclodextrin Self-assembly Molecular dynamics
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.
1543-8384
https://doi.org/10.1021/acs.molpharmaceut.8b01307
10.1021/acs.molpharmaceut.8b01307
Grant Details