Department of Physics, Bernal Institute , University of Limerick , V94 T9PX Limerick , Ireland.
School of Pharmacy, Cavanagh Pharmacy Building , University College Cork , Cork , Ireland.
Mol Pharm. 2019 Mar 4;16(3):1358-1366. doi: 10.1021/acs.molpharmaceut.8b01307. Epub 2019 Feb 19.
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.
功能化环糊精分子在溶液中组装成各种超结构，这对于药物输送和其他纳米材料和生物材料的应用很有意义。在这里，我们使用组合模拟和实验方法来研究 siRNA 和阳离子环糊精（c-CD）衍生物共组装成高度稳定的基因传递纳米结构。c-CD 通过其脂肪尾巴的交错形成超分子结构，类似于脂质双层和胶束的形成。siRNA 的天然构象通过包封的 c-CD 超结构得以保留，在 c-CD 的正电荷侧臂和 siRNA 骨架的负电荷之间形成广泛的氢键网络。通过等温滴定量热法确认了复合物的稳定性，实验/模拟协同设计方法为创建高度可设计的基因传递载体开辟了新途径。
