Novel histidine-conjugated galactosylated cationic liposomes for efficient hepatocyte-selective gene transfer in human hepatoma HepG2 cells

To enhance gene transfection to hepatocytes by cationic liposomes, it is necessary to overcome a number of barriers existing in the process from administration to gene expression. Recently we and other group have demonstrated that the escape of plasmid DNA (pDNA)/cationic liposome complexes (lipople...

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Veröffentlicht in:Journal of controlled release 2007-04, Vol.118 (2), p.262-270
Hauptverfasser: Shigeta, Kosuke, Kawakami, Shigeru, Higuchi, Yuriko, Okuda, Tatsuya, Yagi, Hiroko, Yamashita, Fumiyoshi, Hashida, Mitsuru
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container_end_page 270
container_issue 2
container_start_page 262
container_title Journal of controlled release
container_volume 118
creator Shigeta, Kosuke
Kawakami, Shigeru
Higuchi, Yuriko
Okuda, Tatsuya
Yagi, Hiroko
Yamashita, Fumiyoshi
Hashida, Mitsuru
description To enhance gene transfection to hepatocytes by cationic liposomes, it is necessary to overcome a number of barriers existing in the process from administration to gene expression. Recently we and other group have demonstrated that the escape of plasmid DNA (pDNA)/cationic liposome complexes (lipoplexes) from the endosome to cytoplasm was rate limiting. In this study, to enhance transfection efficiency by promoting the release of lipoplexes from the endosome to cytoplasm, we proposed utilizing the “proton sponge effect”. Here, we synthesized a novel pH-sensitive histidine-modified galactosylated cholesterol derivative (Gal-His-C4-Chol), for a more efficient gene delivery to hepatocytes. Liposomes containing Gal-His-C4-Chol showed much greater transfection activity than conventional Gal-C4-Chol liposomes based on a receptor-mediated mechanism in HepG2 cells. Hence, this finding should contribute to the development of gene therapy using cationic liposomes toward their clinical application.
doi_str_mv 10.1016/j.jconrel.2006.12.019
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subjects Active Transport, Cell Nucleus
Animals
Asialoglycoprotein Receptor - metabolism
Biological and medical sciences
Carcinoma, Hepatocellular - metabolism
Cations
Cell Line, Tumor
Cell Nucleus - metabolism
Cell Survival - drug effects
Cholestenes - metabolism
Cholesterol Esters - chemistry
Cholesterol Esters - metabolism
Cholesterol Esters - toxicity
Cytoplasm - metabolism
DNA - chemistry
DNA - metabolism
Endosomes - metabolism
Galactosylated liposomes
Gene therapy
General pharmacology
Genes, Reporter
Glycopeptides - chemistry
Glycopeptides - metabolism
Glycopeptides - toxicity
Hepatocytes
Histidine
Humans
Hydrogen-Ion Concentration
Liposomes
Liver Neoplasms - metabolism
Luciferases
Mannitol - metabolism
Medical sciences
Mice
NIH 3T3 Cells
Particle Size
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Proton sponge effect
Transfection - methods
title Novel histidine-conjugated galactosylated cationic liposomes for efficient hepatocyte-selective gene transfer in human hepatoma HepG2 cells
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