结合化学通过乙向基于德克斯的输送系统,以控制siRNA的释放
Lina Cui1, Jessica L Cohen, Crystal K Chu
1College of Chemistry, University of California, Berkeley, California 94720-1460, United States.
Journal of the American Chemical Society
|September 11, 2012
概括
新的德克斯结合化学可以通过酸可分裂的乙链接来使药物附着. 这允许在酸性细胞区中控制释放,显示出针对性siRNA输送具有低毒性的承诺.
科学领域:
- 生物结合化学 生物结合化学
- 聚合物科学 聚合物科学
- 药物输送系统 药物输送系统
背景情况:
- 多糖提供生物相容性,但需要功能化治疗应用.
- 开发可控释放系统对于有效的药物输送至关重要.
- 乙链接提供了pH敏感的触发释放机制.
研究的目的:
- 使用可切割的乙烯酸结合物开发多糖类的新型结合化学.
- 创建可调节的多糖基材料,可控制降解和释放速度.
- 设计水溶性siRNA载体,以实现高效和安全的基因沉默.
主要方法:
- 合成具有可调节性质的乙链接的德克斯结合物.
- 乙烯基组的修改以控制立体电子和立体特性.
- 作为siRNA载体的乙烯酸结合氨基dextrans的开发.
- 在体外评估传染效率和细胞毒性.
主要成果:
- 功能部分通过酸可变的乙键成功与德克斯结合.
- 通过修改乙结构来证明可调节的降解和释放动力学.
- 作为有效的siRNA载体,设计了乙烯酸结合的氨基dextrans.
- 在低细胞毒性的情况下实现了高的体外siRNA转染效率.
结论:
- 开发的乙结合化学为多糖功能化提供了一个多功能平台.
- 可调节的乙链接能够精确控制药物释放率,特别是在酸性环境中.
- 乙烯酸结合氨基dextrans代表一个有前途的,安全和高效的系统siRNA交付.
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