聚胺中的基立体化学和氨基数量会影响细胞内DNA的传递
1Department of Chemistry, University of Cincinnati, Cincinnati, Ohio 45221-0172, USA.
Journal of the American Chemical Society
|March 3, 2005
概括
新的聚氨基胺胺显示出作为核酸药物的无毒输送载体的前景. 含有四种二次氨基的聚合物表现出高质粒DNA结合和高效的基因传递,其中G4特别有效.
科学领域:
- 聚合物化学 聚合物化学
- 生物材料科学 生物材料科学
- 基因传递系统是基因传递系统.
背景情况:
- 核酸药物具有治疗潜力,但需要有效和安全的输送系统.
- 现有的配送车辆经常面临有效性和毒性方面的挑战.
- 开发新型聚合物对于推进基于核酸的疗法至关重要.
研究的目的:
- 为了合成和描述用于核酸输送的多糖胺胺的图书馆.
- 系统地研究聚合物结构对等离子体DNA (pDNA) 结合,多重复形成,细胞毒性和基因传递效率的影响.
- 为了确定安全有效的核酸药物输送的最佳聚合物候选者.
主要方法:
- 通过多重凝结合成的多基胺胺 (D1-D4,G1-G4,M1-M4).
- 评估pDNA结合亲和力,pDNA紧缩成纳米颗粒 (多重复),以及各种细胞系中的细胞毒性 (BHK-21,HeLa,HepG2).
- 在体外基因传递研究中,使用记者基因 (露西法酶,β-银酸酶) 和肝素竞争试验.
主要成果:
- 有四种二次氨基 (D4,G4,M4) 的聚合物表现出最高的pDNA结合亲和力.
- 基于银河酸盐的聚合物 (G) 通常形成最小的多复合体.
- 所有合成的poly ((glycoamidoamine) 都表现出有效的pDNA传递,没有细胞毒性;D4,G4和M4显示出最高的效率,G4特别强.
结论:
- 聚胺胺,特别是G4,代表了核酸药物的有希望的无毒输送载体.
- 较高的pDNA结合亲和力与增强的基因传递效率相关,可能通过防止过早的多重复分离.
- 聚氨基胺胺的结构修改可以量身定制,以优化核酸输送性能.
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