Polyelectrolyte Complexes : Linking Chemistry and Structure to Biological Function

聚电解质复合物：将化学和结构与生物功能联系起来

• 批准号: 204990-2013
• 负责人: Buschmann, Michael
• 金额: $ 3.21万
• 依托单位: École Polytechnique de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=570028
• 关键词: Polyelectrolyte; Complexes; Linking; Chemistry; Structure

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. The overall objective is to provide design principles and elucidate mechanisms of biological function for efficient and non-toxic chitosan/nucleic acid delivery vehicles for gene expression/knockdown, recombinant protein production and in vivo applications in animals and humans. A vast number of studies are performed worldwide on nanoparticle systems for the intracellular delivery of nucleic acids generating increased knowledge of their function and biological effects. Nonetheless many studies are descriptive with only a minority revealing basic mechanisms that can be used to identify further systems which can be effective and safe. This proposal aims to extend our recent work where basic principles relating chemical and structural properties of polyelectrolyte complexes to their ability to effectively deliver nucleic acids to intracellular sites of action will be advanced. The results will be significant for the fields of nanotechnology and cell biology.

聚电解质复合物是通过聚阳离子和聚苯翁之间的静电吸引力形成的纳米颗粒。当聚会是DNA或RNA等核酸序列时，这些系统的特定类别用于将遗传物质引入细胞中。我们已经使用多阳离子壳聚糖（一种自然的葡萄糖聚合物聚合物）研究了这些递送系统，该聚合物是部分乙酰化的，而质粒DNA则在传递到核时表达基因。我们还开发了含有siRNA的纳米颗粒，这些siRNA停止了靶基因的表达。除了评估细胞内摄取，几种细胞类型的细胞内运输和转基因表达外，这些系统使用定制生产的壳聚糖和一系列物理化学和结构表征方法的某些机制有效地阐明了这些系统，并使用了一系列的聚合物和产生的纳米结构的物理化学和结构表征方法。该建议旨在进一步阐明可以实现有效和无毒的核酸递送到细胞中的基本机制。 总体目标是提供设计原理，并阐明生物学功能的机制，以提供有效和无毒的壳聚糖/核酸递送车辆，用于基因表达/敲低，重组蛋白质产生以及在动物和人类中的体内应用。全世界在纳米颗粒系统上进行了大量研究，用于核酸的细胞内递送，从而增加了对其功能和生物学作用的了解。但是，许多研究具有描述性，只有少数揭示了基本机制，这些机制可用于识别可以有效且安全的进一步系统。该建议旨在扩展我们最近的工作，其中将聚电解质复合物的化学和结构特性与它们有效将核酸输送到细胞内作用位点的能力相关的基本原理。结果对于纳米技术和细胞生物学领域将很重要。