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聚三醇:覆盖糖的纳米复合物促进稳定和有效的多重复合介导siRNA传递
Antons Sizovs1, Lian Xue, Zachary P Tolstyka
1Department of Chemistry and Macromolecules and Interfaces Institute, Virginia Tech , Blacksburg, Virginia 24060, United States.
Journal of the American Chemical Society
|October 3, 2013
概括
聚 ((三) 涂层增强纳米颗粒的稳定性和为siRNA输送的细胞吸收. 这种新型聚合物在冷干燥过程中保护核酸,并改善低毒性质母细胞细胞中治疗性基因沉默.
科学领域:
- 材料科学 材料科学 材料科学
- 生物技术是生物技术.
- 聚合物化学 聚合物化学
背景情况:
- 纳米粒子表面特性决定了环境相互作用.
- 一种分糖体的三糖提供独特的生物稳定效果.
- 开发用于增强纳米粒子功能的新型聚合物对纳米医学至关重要.
研究的目的:
- 合成和表征多甲基胺三醇 (多甲基胺三醇) 和其与氨基甲基胺 (AEMA) 的双块共聚物.
- 评估聚三醇涂层在稳定siRNA多复合体和促进细胞内化方面的有效性.
- 评估聚三糖作为治疗纳米粒子配方成分的潜力.
主要方法:
- 合成聚三和基于AEMA的双块共聚.
- 在高盐和血清条件下评估siRNA多复合体的合稳定性.
- 对siRNA多重复合体的冷干燥保护和再悬浮的评估.
- 共聚焦显微镜用于研究聚三醇涂层多重复合体的细胞内化和贩运.
- 确定siRNA诱导的基因下调和IC50值.
主要成果:
- 聚 ((三醇) 涂层在具有挑战性的条件下确保siRNA多复合体的合体稳定性.
- 该聚合物在冷干燥过程中保护siRNA多重复合体,允许在没有功能损失的情况下完全重新悬浮.
- 覆盖着多甲醇的siRNA多复合体通过零阶动力学表现出高效的细胞内化到质母细胞细胞中.
- 实现了控制的siRNA传递和显著的目标基因下调 (IC50 = 19 nM).
- 对于涂有聚三醇的纳米颗粒,观察到微不足道的细胞毒性.
结论:
- 聚三) 是稳定治疗纳米粒子配方的有希望的聚合物.
- 涂层增强细胞吸收和核酸的输送.
- 聚三) 显示了纳米医学应用的潜力,包括核酸输送和其他纳米技术.
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