聚化β-cyclopodextrin"点击集群":用于核酸输送的单分散和多功能支架
Sathya Srinivasachari1, Katye M Fichter, Theresa M Reineke
1Department of Chemistry, University of Cincinnati, Cincinnati, Ohio 45221-0172, USA.
Journal of the American Chemical Society
|March 15, 2008
概括
新型β-环极素"点击集群"有效地将治疗性等离子体DNA (pDNA) 输送到细胞中. 这些无毒的多化载体对基因疗法应用有前途,其优化结构显示出高疗效和低细胞毒性.
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:
- 开发高效和安全的非病毒载体用于治疗等离子体DNA (pDNA) 输送对于基因疗法至关重要.
- 基于β-cyclodextrin的支架具有生物相容性和多价值性,使其对药物输送应用具有吸引力.
研究的目的:
- 为了合成和描述新型多价值的多化β-cyclodextrin.
主要方法:
- 通过铜催化的1,3-双极循环添加合成β-循环德克斯特林点击集群.
- 使用凝电泳,动态光散射和传输电子显微镜进行表征.
- 在体外评估pDNA复杂化,核酶保护,细胞吸收,基因表达和细胞毒性.
主要成果:
- 合成的点击集群有效地将pDNA复杂化和压缩成纳米粒子 (80-130nm).
- 聚合物保护pDNA免受核酶降解,在血清中观察到长达48小时的显著保护.
- 化合物9d和9e在HeLa和H9c2细胞中表现出高的细胞吸收和基因传递效率,与商业转染剂相当.
- 基因表达水平与集群手臂中的橄乙烯胺单元数量呈正相关.
- 所有合成的点击集群都表现出低细胞毒性,与商业对照的高毒性 (Jet-PEI和Superfect) 相比.
结论:
- 基于β-cyclodextrin的新型点击集群是有效且无毒的pDNA载体.
- 化合物9d和9e是基因治疗进一步发展的有希望的候选物.
- 设计策略允许调节性质,为优化系统性交付车辆铺平道路.
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