A click chemistry route to 2-functionalised PEGylated and cationic β-cyclodextrins: co-formulation opportunities for siRNA delivery.
A click chemistry route to 2-functionalised PEGylated and cationic β-cyclodextrins: co-formulation opportunities for siRNA delivery.
复制标题
DOI：
10.1039/c2ob25490e
复制
发表时间：
2012-06
影响因子：
3.2
通讯作者：
A. O’Mahony;J. Ogier;Stéphane Desgranges;J. Cryan;R. Darcy;C. O’Driscoll
中科院分区：
文献类型：
--
作者：
A. O’Mahony;J. Ogier;Stéphane Desgranges;J. Cryan;R. Darcy;C. O’Driscoll
一种合成两亲性 β-环糊精的新方法使用“点击”化学来选择性地修饰仲 2-羟基。所得延伸的极性基团可以是聚阳离子基团或中性聚乙二醇化基团，并且这两种两亲物类别在用于递送siRNA的双环糊精制剂中是相容的。当与 siRNA 单独使用时，阳离子环糊精在细胞培养物中显示出良好的转染特性。与聚乙二醇化环糊精的共配制改变了用 siRNA 形成的纳米颗粒的物理化学性质。改进的颗粒特性包括较低的表面电荷和减少的聚集倾向。然而，正如预期的那样，阳离子载体的转染效率因与聚乙二醇化环糊精共配制而降低，需要未来用靶向配体对颗粒进行表面修饰以实现有效的 siRNA 递送。
A new approach to the synthesis of amphiphilic β-cyclodextrins has used 'click' chemistry to selectively modify the secondary 2-hydroxyl group. The resulting extended polar groups can be either polycationic or neutral PEGylated groups and these two amphiphile classes are compatible in dual cyclodextrin formulations for delivery of siRNA. When used alone with an siRNA, a cationic cyclodextrin was shown to have good transfection properties in cell culture. Co-formulation with a PEGylated cyclodextrin altered the physicochemical properties of nanoparticles formed with siRNA. Improved particle properties included lower surface charges and reduced tendency to aggregate. However, as expected, the transfection efficiency of the cationic vector was lowered by co-formulation with the PEGylated cyclodextrin, requiring future surface modification of particles with targeting ligands for effective siRNA delivery.