Asialoglycoprotein receptor targeted gene delivery using galactosylated polyethylenimine-graft-poly(ethylene glycol): In vitro and in vivo studies

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Title
Asialoglycoprotein receptor targeted gene delivery using galactosylated polyethylenimine-graft-poly(ethylene glycol): In vitro and in vivo studies
Author(s)
E M Kim; H J Jeong; I K Park; C S Cho; H B Moon; Dae Yeul Yu; H S Bom; M H Sohn; I J Oh
Bibliographic Citation
Journal of Controlled Release, vol. 108, no. 2, pp. 557-567
Publication Year
2005
Abstract
The asialoglycoprotein receptor (ASGP-R) on the hepatocyte membrane is a specific targeting marker for gene and drug delivery. Polyethylenimine (PEI) is a polycationic nonviral vector that is used for gene transfer. We have synthesized galactosylated polyethylenimine-graft-poly(ethylene glycol) (GPP) for performing gene delivery to the hepatocytes. The present study reports on the in vitro and in vivo data that was achieved in hepatoma bearing transgenic mice. The cytotoxicity was decreased with the increasing PEG content. The particle size of the complex was increased with the increasing PEG at an N / P ratio of 3.0, while the zeta potentials were decreased. The 99mTc labeled complexes were transfected into HepG2 and HeLa cells, while the GFP reporter genes were mainly expressed in the HepG2 cells. The in vivo data was achieved in ALB/c-Ha-ras transgenic mice. 99mTc labeled GPP 50/DNA was injected into the mice via the tail vein, and the gamma images were acquired at 5, 15 and 30 min. The 99mTc labeled complexes were mainly localized in the heart and liver, and they were excreted through the kidneys. The GFP gene was mainly expressed in the proliferating cells at the tumor periphery. This result was confirmed by PCNA staining. The GPP 50/DNA complexes were bound to ASGP-R of the proliferating hepatocytes in vitro and in vivo. The present results demonstrate the feasibility of nonviral gene transfer using galactosylated PEI-PEG in vivo.
Keyword
Asialoglycoprotein receptorHepatocellular carcinoma animal modelPolyethylenimineTechnetium-99m
ISSN
0168-3659
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.jconrel.2005.09.001
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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