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Self-Assembled Cationic β-Cyclodextrin Nanostructures for siRNA Delivery.

Raghvendra Pratap SinghTania HidalgoPierre-Andre CazadeRaphael DarcyMichael F CroninIrina DorinCaitríona M O'DriscollDamien Thompson
Published in: Molecular pharmaceutics (2019)
Functionalized 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 coassembly 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 side arms of c-CD and the negatively charged siRNA backbone. The stability of the complexation is confirmed using isothermal titration calorimetry, and the experimental/simulation codesign methodology opens new avenues for creation of highly engineerable gene delivery vectors.
Keyphrases
  • cancer therapy
  • drug delivery
  • hyaluronic acid
  • nk cells
  • ionic liquid
  • molecular dynamics simulations
  • quantum dots
  • high resolution
  • capillary electrophoresis
  • fatty acid