针对神经元的共聚合物具有可脱落的屏蔽块,使用可减少的RAFT-ATRP双头剂合成
Hua Wei1, Joan G Schellinger, David S H Chu
1Department of Bioengineering and Molecular Engineering and Sciences Institute, University of Washington, Seattle, Washington 98195, USA.
Journal of the American Chemical Society
|September 28, 2012
概括
开发新的聚合物基因传递系统对于体内应用至关重要. 这项研究介绍了一种阻断共聚物,通过结合准,可逆屏蔽和内体释放能力来提高基因传递效率.
科学领域:
- 生物材料科学 生物材料科学
- 基因治疗 基因治疗
- 聚合物化学 聚合物化学
背景情况:
- 在体外将基因输送系统适应在体内使用是具有挑战性的,因为固态稳定会损害转染效率.
- 现有系统通常需要在体外应用中进行稳定,这导致效率相比体外性能降低.
研究的目的:
- 开发一种多功能区块共聚合物,用于有效的体内基因传递.
- 创建一个能够克服稳定性和转化效率之间的权衡的系统.
主要方法:
- 用一种新型的双头剂进行受控聚合,合成一个明确的阴离子块共聚合物.
- 形成具有细胞向特征的DNA纳米颗粒,可逆屏蔽和内体细胞逃逸.
- 在多种哺乳动物细胞系 (包括神经元类细胞) 中进行体外传染研究,以评估效率.
主要成果:
- 合成的块共聚合物形成盐稳定颗粒,凝结等离子体DNA.
- 可逆屏蔽的多重复合物表现出比稳定屏蔽的聚合物高出10倍的传染效率.
- 向和稳定颗粒保持了与非稳定配方相比的转化效率.
结论:
- 开发的区块共聚合物系统通过平衡稳定和转染效率,为体内基因传递提供了一个有前途的解决方案.
- 结合可逆屏蔽和细胞特异向,可以提高稳定颗粒中的基因传递性能.
- 这些先进的聚合物载体显示出在体内安全有效的基因治疗应用的潜力.
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