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Self-assembled cationic #-cyclodextrin nanostructures for siRNA delivery
Date
2019
Abstract
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.
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Description
peer-reviewed
Publisher
American Chemical Society
Citation
Molecular Pharmaceutics;16 (3), pp. 1358-1366
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Funding Information
Science Foundation Ireland (SFI), Higher Education Authority (HEA), Enterprise Ireland (EI), European Research Council (ERC)