期刊
ACS NANO
卷 9, 期 3, 页码 2405-2419出版社
AMER CHEMICAL SOC
DOI: 10.1021/nn505166x
关键词
protein corona; targeted delivery; retinol; drug nanocarriers; hepatic fibrosis
类别
资金
- National Science Fund for Distinguished Young Scholars [81025019]
- National Basic Research Program of China [2012CB517603]
- National High Technology Research and Development Program of China [2014AA020707]
- Program for New Century Excellent Talents in University [NCET-13-0272]
- National Natural Science Foundation of China [31271013, 31170751, 31200695, 31400671, 51173076, 91129712, 81102489]
- Key Project of the Chinese Ministry of Education [108059]
- Ph.D. Programs Foundation of the Ministry of Education of China [20100091120020, 20130091110037]
- Nanjing University State Key Laboratory of Pharmaceutical Biotechnology Open Grant [KF-GN-201409, 02ZZYJ-201307]
- Science and Technology Development Fund, Macao [FDCT 048/2013/A2]
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 (AS0)-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 AS0-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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