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Baiqiu Chen1, Qidi Ren1, Pingge Jiang1
1College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, Zhejiang, 310014, China.
Macromolecular bioscience
|July 25, 2024
概括
新的可生物降解聚合物称为聚 (β-氨基) (PBAE) 具有疏水终端显示提供siRNA的承诺. 某些PBAE载体在低细胞毒性下实现高基因淘汰,为先进的治疗提供了潜力.
科学领域:
- 生物材料科学 生物材料科学
- 纳米技术 纳米技术
- 基因治疗 基因治疗
背景情况:
- 聚 (β-氨基) (PBAE) 是可生物降解的聚合物,被研究为小干扰RNA (siRNA) 的阴离子载体.
- 目前的PBAE载体通常使用水友性或带电氨酸进行终止,从而限制了它们的传递潜力.
- 在PBAE载体上的疏水终端组代表了优化siRNA递送的未经探索的领域.
研究的目的:
- 构建和选一个由168个PBAE聚合物组成的新平台,配有疏水性基链终端,用于siRNA输送.
- 为了确定有效的PBAE载体,降低细胞毒性和增强基因淘汰效率.
- 研究PBAE结构,pKa和与辅助脂质共同配制对siRNA递送的影响.
主要方法:
- 通过顺序的aza-Michael添加合成PBAE聚合物平台 (168种变体),具有疏水性基链末端.
- 在PBAE聚合物的体外查,以检测siRNA传递效率 (siLuc) 和HeLa-Luc细胞中的细胞毒性.
- 分析PBAE结构,pKa和输送性能之间的关系;评估与辅助脂质的共同配制.
主要成果:
- PA8-C6和PA8-C8 PBAE携带者表现出显著的基因淘汰 (高达80%),细胞毒性低.
- 某些PA2和PA5系列PBAE材料显示出强烈的siRNA输送,但与更高的细胞毒性有关.
- PBAE pKa主要由侧链决定 (与PA8疗效相关的≈6.2-6.5范围);与辅助脂质共同配制减少了颗粒大小,表面电荷,并改善了递送/降低了毒性.
结论:
- 疏水终结的PBAE聚合物为有效和安全的siRNA输送提供了一个有前途的平台.
- 特定的PBAE结构,如PA8-C6和PA8-C8,显示出用于基因淘汰应用的绝佳潜力.
- 使用辅助脂质优化PBAE载体设计和配方,可以显著提高治疗疗效,降低基因传递系统中的毒性.
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