基于胰岛素的纳米颗粒用于在急性损伤中向siRNA输送
Chinmay M Jogdeo1, Sudipta Panja1, Neha Kumari1
1Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA.
概括
一种新型的胰岛素-CPTA聚合物向受伤的脏,输送siRNA使p53沉默,并改善小鼠急性损伤 (AKI) 的结果. 这种向的RNA输送减少了损伤并增强了功能.
科学领域:
- 生物材料科学 生物材料科学
- 纳米医学是一种纳米医学.
- 脏生理学 脏生理学
背景情况:
- RNA干扰 (RNAi) 在急性损伤 (AKI) 中显示出治疗前景.
- 有效地将RNA治疗药物输送到脏仍然是一个挑战.
- 一种多糖类的胰岛素因其脏向潜力而被探索.
研究的目的:
- 开发一种新的脏向聚合物,用于选择性siRNA输送到AKI中受伤脏.
- 在临床前AKI模型中研究通过新型聚合物传递的p53-向siRNA的治疗疗效.
主要方法:
- 通过将α-cyclam-p-toluic acid (CPTA) 与inulin结合,合成胰岛素-CPTA (IC) 聚合物.
- 形成IC/siRNA纳米颗粒 (复合体) 进行有针对性的输送.
- 评估纳米粒子积累,细胞吸收和p53沉默在西斯诱导的AKI小鼠.
- 评估治疗结果,包括功能,损伤标志物和炎症.
主要成果:
- 在受伤的脏中选择性积累的胰岛素-CPTA纳米颗粒,准CXCR4过度表达的细胞.
- 在受损的管中,IC/siRNA多重复体表现出高效的吸收和长时间的保留.
- 对IC/p53siRNA纳米颗粒的系统性给药在AKI脏中强烈地抑制了p53表达.
- 在小鼠中,选择性p53敲击显著降低了管状细胞死亡,炎症,并改善了功能.
结论:
- 胰岛素-CPTA是一种有前途的生物降解载体,可用于向脏的siRNA治疗药物.
- 这种向RNA输送方法为治疗急性损伤提供了潜在的新策略.
- IC聚合物促进受伤脏的选择性基因沉默,从而改善治疗结果.
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