Encapsidation of RNA-Polyelectrolyte Complexes with Amphiphilic Block Copolymers: Toward a New Self-Assembly Route
Encapsidation of RNA-Polyelectrolyte Complexes with Amphiphilic Block Copolymers: Toward a New Self-Assembly Route
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DOI：
10.1021/ja310397j
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发表时间：
2012-12-12
影响因子：
15
通讯作者：
Schatz, Christophe
中科院分区：
文献类型：
--
作者：
Bui, Laurent;Abbou, Scarlette;Schatz, Christophe
两亲性嵌段共聚物是由亲水和疏水链段组成的分子，具有自发自组装成各种超分子结构如胶束和囊泡的能力。在这里，我们提出了一种新颖的方法来自组装成一个支持的双层膜的纳米粒子涂层的两亲性嵌段共聚物。该方法的核心在于共聚物的两亲性的变化，这种变化可以通过改变溶剂的极性来关闭和打开。在这种条件下，组装过程可以利用有机溶剂和水中的特定分子相互作用。虽然这一概念可能适用于任何类型的带电基质，但我们的兴趣集中在设计一种新型的模拟病毒形态的聚合物组装体上。一个类似于胶囊壳的糖蛋白模拟两亲性嵌段共聚物自组装周围的siRNA和聚乙烯亚胺的带正电荷的复合物。这个过程需要两个步骤。嵌段共聚物首先通过静电相互作用与分散在DMSO中的复合物相互作用。接下来，介质中的水含量的增加触发疏水效应和伴随的自由嵌段共聚物分子在复合物表面自组装成双层膜。共聚物修饰的复合物相对于单独的复合物的更高的基因沉默活性显示了这种新型纳米结构用于生物应用的潜力，特别是用于递送治疗性生物分子。
Amphiphilic block copolymers are molecules composed of hydrophilic and hydrophobic segments having the capacity to spontaneously self-assemble into a variety of supramolecular structures like micelles and vesicles. Here, we propose an original way to self-assemble amphiphilic block copolymers into a supported bilayer membrane for defined coating of nanoparticles. The heart of the method rests on a change of the amphiphilicity of the copolymer that can be turned off and on by varying the polarity of the solvent. In this condition, the assembly process can take advantage of specific molecular interactions in both organic solvent and water. While the concept potentially could be applied to any type of charged substrates, we focus our interest on the design of a new type of polymer assembly mimicking the virus morphology. A capsid-like shell of glycoprotein-mimic amphiphilic block copolymer was self-assembled around a positively charged complex of siRNA and polyethyleneimine. The process requires two steps. Block copolymers first interact with the complexes dispersed in DMSO through electrostatic interactions. Next, the increase of the water content in the medium triggers the hydrophobic effect and the concomitant self-assembly of free block copolymer molecules into a bilayer membrane at the complex surface. The higher gene silencing activity of the copolymer-modified complexes over the complexes alone shows the potential of this new type of nanoconstructs for biological applications, especially for the delivery of therapeutic biomolecules.