活性向siRNA输送的瘤酸性敏感聚合物载体
Chun-Yang Sun1, Song Shen1, Cong-Fei Xu2
1The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China , Hefei, Anhui 230027, PR China.
Journal of the American Chemical Society
|November 17, 2015
概括
新的纳米导体会在瘤中脱离它们的保护,从而增强siRNA的传递. 这种方法克服了PEGylation
科学领域:
- 生物医学工程
- 纳米技术
- 提供药物
背景情况:
- siRNA载体的表面PEGylation阻止了蛋白质吸附和RES清除,但阻碍了细胞吸收.
- 能够响应刺激的,可脱离外的纳米导体为增强细胞内化和延长血液循环提供了解决方案.
- 瘤细胞外pH值 (pHe) 是一个有前途的刺激,但由于微妙的pH值差异,设计敏感系统具有挑战性.
研究的目的:
- 开发一种新型的敏感酸桥合聚合物,用于针对瘤的全身传递siRNA.
- 创建刺激反应的纳米导体, 增强细胞吸收,
- 克服PEGylation对siRNA载体性能双重影响的困境.
主要方法:
- 开发一种简单的敏感酸桥合聚合物.
- 用聚乙烯糖醇 (PEG) 冠状形成微粒传递系统 (Dm-NP).
- 结合PEG脱落的pH响应链和细胞透来增强吸收.
主要成果:
- 在长期循环和RES逃逸方面,Dm-NP显示稳定的PEG冠状体.
- 在瘤部位的酸敏感连接断裂引发了PEG脱离,促进了细胞向.
- 在移除PEG时暴露细胞透显著增强了细胞吸收.
- Dm-NP可以有效地抑制瘤积累,并增强非小细胞肺癌的生长.
结论:
- 开发的Dm-NP系统成功地平衡了长时间的血液循环和向的细胞输送.
- 响应刺激的PEG脱离是增强纳米导体在瘤中的有效性的可行策略.
- 这种方法为siRNA输送和癌症治疗提供了安全有效的方法.
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