Polyelectrolyte Complexes : Linking Chemistry and Structure to Biological Function

聚电解质络合物是通过聚阳离子和聚阴离子之间的静电吸引而形成的纳米颗粒。当多阴离子是DNA或RNA之类的核酸序列时，这类特殊的系统被用来将遗传物质引入细胞。我们使用聚阳离子壳聚糖(一种部分乙酰化的氨基葡萄糖的天然聚合物)和质粒DNA研究了这些递送系统，当递送到细胞核时，表达基因。我们还开发了含有siRNA的纳米颗粒，可以阻止目标基因的表达。除了评估几种细胞类型的细胞摄取、细胞内运输和转基因表达外，这些系统有效发挥作用的某些机制已经通过一系列定制的壳聚糖和一系列聚合物及其纳米结构的物理化学和结构表征方法来阐明。这一建议旨在进一步阐明有效和无毒地将核酸输送到细胞内的基本机制。

Polyelectrolyte complexes are nanoparticles that form via electrostatic attraction between a polycation and polyanion. A particular class of these systems is used to introduce genetic material into cells when the polyanion is a nucleic acid sequence like DNA or RNA. We have studied these delivery systems using the polycation chitosan, a natural polymer of glucosamine that is partly acetylated, and plasmid DNA to express genes when delivered to the nucleus. We have also developed nanoparticles containing siRNA which stop expression of the target gene. Certain mechanisms by which these systems function efficiently have been elucidated using a family of custom-produced chitosans and a battery of physicochemical and structural characterization methods of the polymers and resulting nanostructures, in addition to assessment of cell uptake, intracellular trafficking and transgene expression in several cell types. This proposal aims to further elucidate the fundamental mechanisms by which effective and non-toxic delivery of nucleic acids into cells can be achieved.