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: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=546432
• 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.

聚电解质复合物是通过聚阳离子和聚阴离子之间的静电吸引形成的纳米颗粒。当聚阴离子是核酸序列如DNA或RNA时，这些系统中的特定类别用于将遗传物质引入细胞。我们研究了这些传递系统使用聚阳离子壳聚糖，一种天然聚合物的葡萄糖胺，部分乙酰化，和质粒DNA表达基因时，交付到细胞核。我们还开发了含有siRNA的纳米颗粒，可以阻止靶基因的表达。这些系统有效地发挥作用的某些机制已被阐明，使用一个家庭的定制生产的壳聚糖和电池的聚合物和所得的纳米结构的物理化学和结构表征方法，除了在几种细胞类型中的细胞摄取，细胞内运输和转基因表达的评估。该提议旨在进一步阐明可以实现将核酸有效且无毒地递送到细胞中的基本机制。