title: Corona-directed nucleic acid delivery into hepatic stellate cells for liver fibrosis therapy.
abstract: 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.
authors.affiliation: †State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: ‡State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR, China.
authors.forename: Chunming
authors.initials: C
authors.lastname: Wang
authors.affiliation: †State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Yinhe
authors.initials: Y
authors.lastname: Zha
authors.affiliation: †State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.affiliation: †State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Zhongfei
authors.initials: Z
authors.lastname: Gao
authors.affiliation: †State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Zang
authors.affiliation: †State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Jiangning
authors.initials: J
authors.lastname: Chen
authors.affiliation: †State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: †State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Dong
mesh_terms: D000418:Albumins / Q000737:chemistry; D000818:Animals; D002460:Cell Line; D004337:Drug Carriers / Q000737:chemistry*; D055166:Hepatic Stellate Cells / Q000378:metabolism*; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D016376:Oligonucleotides, Antisense / Q000737:chemistry* / Q000235:genetics* / Q000493:pharmacokinetics; D011094:Polyethyleneimine / Q000737:chemistry; D000066970:Protein Corona / Q000737:chemistry*; D012177:Retinol-Binding Proteins / Q000737:chemistry; D014018:Tissue Distribution; D014162:Transfection; D014801:Vitamin A / Q000737:chemistry
chemical_list: D000418:Albumins; D004337:Drug Carriers; D016376:Oligonucleotides, Antisense; D000066970:Protein Corona; D012177:Retinol-Binding Proteins; D014801:Vitamin A; D011094:Polyethyleneimine
keywords: drug nanocarriers; hepatic fibrosis; protein corona; retinol; targeted delivery