肝星状细胞
肝纤维化
药物输送
纤维化
体内
基因传递
化学
毒品携带者
遗传增强
癌症研究
肝纤维化
生物物理学
细胞生物学
医学
心脏纤维化
纳米技术
核酸
药理学
生物化学
生物
材料科学
病理
基因
生物技术
作者
Zhengping Zhang,Chunming Wang,Yinhe Zha,Wei Hu,Zhong-Fei Gao,Yuhui Zang,Jiangning Chen,Junfeng Zhang,Lei Dong
出处
期刊:ACS Nano
[American Chemical Society]
日期:2015-01-16
卷期号:9 (3): 2405-2419
被引量:95
摘要
Strategies to modify nanoparticles with biological ligands for targeted drug delivery in vivo have been widely studied but met with limited clinical success. A possible reason is that, in the blood circulation, serum proteins could rapidly form a layer of protein “corona” on the vehicle surface, which might block the modified ligands and hamper their targeting functions. We speculate that strategies for drug delivery can be designed based upon elegant control of the corona formation on the vehicle surfaces. In this study, we demonstrate a retinol-conjugated polyetherimine (RcP) nanoparticle system that selectively recruited the retinol binding protein 4 (RBP) in its corona components. RBP was found to bind retinol, and direct the antisense oligonucleotide (ASO)-laden RcP carrier to hepatic stellate cells (HSC), which play essential roles in the progression of hepatic fibrosis. In both mouse fibrosis models, induced by carbon tetrachloride (CCl4) and bile duct ligation (BDL), respectively, the ASO-laden RcP particles effectively suppressed the expression of type I collagen (collagen I), and consequently ameliorated hepatic fibrosis. Such findings suggest that this delivery system, designed to exploit the power of corona proteins, can serve as a promising tool for targeted delivery of therapeutic agents for the treatment of hepatic fibrosis.
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