Feasibility on systemic delivery of asialoorosomucoid complex to hepatic origin cells mediated by asialoglycoprotein receptor

Abstract

Receptor mediated gene delivery is a new gene transfer strategy. Asialoglycoprotein receptor (ASGP-R), the receptor of asialoorosomucoid (Asor), is specially expressed on the surface of hepatocyte. In this paper, the nuclide¹³¹I was combined with Asor to form a kind of soluble nuclide-protein complex, which can be specifically endocytosed into hepatocyte by ASGP-R. After intravenous injection of the complex into experimental animals, the deposition of Asorin vivo and the targeting quality of hepatocyte was detected by ECT. This research testified the feasibility of targeting Asor complex delivery to hepatocyte mediated by ASGP-Rin vivo, and provided foundation for the genetic diagnosis and gene therapy of hepatic cell-related diseases.

Keywords

asialoglycoprotein receptor / receptor imaging / vp3 gene / hepatocellular carcinoma

References

[1] NguyenT H, FerryN. Liver gene therapy: advances and hurdles. Gene Ther, 2004, 11(Suppl 1): 76-76

[2] ZhaoX B, LeeR J. Tumor-selective targeted delivery of genes and antisense oligodeoxyribonucleotides via the folate receptor. Adv Drug Deliv Rev, 2004, 56(8): 1193-1193

[3] StefanidakisM, KoivunenE. Peptide-mediated delivery of therapeutic and imaging agents into mammalian cells. Curr Pharm Des, 2004, 10(24): 3033-3033

[4] GustT C, ZenkeM. Receptor-mediated gene delivery. Sci World J, 2002, 2: 224-224

[5] WuJ, NantzM H, ZernM A. Targeting hepatocytes for drug and gene delivery: emerging novel approaches and applications. Front Biosci, 2002, 7: d717-d717

[6] WuC H, WuG Y. Receptor-mediared delivery of foreign genes to hepatocytes. Adv Drug Deliv Rev, 1998, 29(3): 243-243

[7] SinghM, KisoonN, AriattiM. Receptor-mediated gene delivery to HepG2 cells by ternary assemblies containing cationic liposomes and cationized asialoorosomucoid. Drug Deliv, 2001, 8(1): 29-29

[8] SinghM, AriattiM. Targeted gene delivery into HepG2 cells using complexes containing DNA, cationized asialoorosomucoid and activated cationic liposomes. J Control Release, 2003, 92(3): 383-383

[9] ZhangY X. Experimental Nuclear Medicine, 2002, Beijing, Peoples Healthy Press: 160-165

[10] SunX H, TanL, LiC Y, et al.. A novel gene delivery system targeting urokinase receptor. Acta Biochim Biophys Sin, 2004, 36(7): 485-485

[11] EisenburgC, SetaN, AppelM, et al.. Asialoglycoprotein receptor in human isolated hepatocytes from normal liver and its apparent increase in liver with histological alterations. J Hepatol, 1991, 13: 305-305