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Title 

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

Authors 

E M KimH J JeongI K ParkC S ChoH B MoonDae Yeul YuH S BomM H SohnI J Oh

Publisher 

Elsevier

Issue Date 

2005

Citation 

Journal of Controlled Release, vol. 108, no. 2, pp. 557-567

Keywords 

asialoglycoprotein receptorhepatocellular carcinoma animal modelpolyethyleniminetechnetium-99mgenetic engineeringpolyethylene glycolsasialoglycoprotein receptorsgenesgalactosylated polyethylenimine

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.

ISSN 

0168-3659

Link 

http://dx.doi.org/10.1016/j.jconrel.2005.09.001

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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