Liver-targeted gene transfer into a human hepatoblastoma cell line and in vivo by sterylglucoside-containing cationic liposomes

Hwang, Sung Hee; Hayashi, Kyoko; Takayama, Kozo; Maitani, Yoshie

doi:10.1038/sj.gt.3301510

Cited by 40 publications

(18 citation statements)

References 28 publications

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“…8,15) In both lipoplexes, the highest gene expression was observed at a charge ratio (Ϫ : ϩ) of 1.0 : 2.3 and transfection efficacy was reduced at higher charge ratios. This observation agrees with the previous reports about conventional lipoplex in various types of cells, 16,17) sterylglucoside-containing lipoplex in HepG2 cells, 18) and mannosylated lipoplex in macrophages by the uptake of mannose receptor. 19) As shown in Fig.…”

Section: Discussionsupporting

confidence: 83%

Intracellular Trafficking Is the Important Process That Determines the Optimal Charge Ratio on Transfection by Galactosylated Lipoplex in HepG2 Cells

Saito

Kawakami

Yabe

et al. 2006

Biological & Pharmaceutical Bulletin

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Non-viral vectors have advantages in terms of their simplicity of use and ability to be produced on a large scale if necessary. Among various types of non-viral vectors, cationic liposome-mediated gene transfection is one of the most promising approaches due to the high transfection efficiency. [1][2][3][4] Gene delivery to hepatocytes is of great therapeutic potential, since the cells are responsible for the synthesis of a wide variety of proteins that play important biological roles both inside and outside the liver. To achieve targeted gene delivery to hepatocytes, galactose has been shown to be a promising targeting ligand because these cells possess a large number of asialoglycoprotein receptors that recognize the galactose units on the synthetic galactosylated carriers. 5-7)Recently, we have developed galactosylated cationic liposomes containing cholesten-5-yloxy-N-(4-((1-imino-2-Dthiogalactosylethyl)amino)butyl)formamide (Gal-C4-Chol) for hepatocyte-selective gene transfection via asialoglycoprotein receptor-mediated endocytosis after intraportal administration into mice. [8][9][10] In this approach, plasmid DNA is mixed with preformed galactosylated cationic liposomes to form galactosylated lipoplex, based on electrostatic interaction, which can then interact with hepatocytes and be taken up by them. Since Gal-C4-Chol possesses an imino group for binding to plasmid DNA via electrostatic interaction, many galactose units can be introduced on the liposomal surface without loss of binding affinity to plasmid DNA. These promising properties of our galactosylated lipoplex enable hepatocyte-selective gene transfer to be achieved under in vivo conditions. The overall ratio of the positive charge on a cationic lipid to the negative charge on a plasmid DNA seems to be a critical determinant of this phenomenon. It is generally accepted that the physicochemical characteristics of the galactosylated lipoplex prepared at different mixing ratios are so different that their cellular uptake, subsequent intracellular trafficking and resultant transfection efficiency would be significantly affected. However, there is little published information on the relationship between these physicochemical and biological factors in the lipoplex and/or galactosylated lipoplex.Previously, we have investigated the effect of the pDNA-N- [1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA)/dioleoylphosphatidylethanolamine (DOPE) liposomes mixing (charge) ratio on the particle size, zeta potential and structure of the lipoplex, which directly affects cellular uptake, intracellular distribution of the complex, and the subsequent gene expression efficiency. And we have demonstrated that the mixing (charge) ratio of plasmid DNA complexed with DOTMA/DOPE liposomes significantly affects the intracellular trafficking, which is an important determinant of the optimal charge ratio in cationic liposome-mediated transfection.11) The in vivo gene transfection efficacy by lipoplex was markedly affected by the type of neutral lipid. Prev...

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Section: Discussionsupporting

confidence: 83%

Intracellular Trafficking Is the Important Process That Determines the Optimal Charge Ratio on Transfection by Galactosylated Lipoplex in HepG2 Cells

Saito

Kawakami

Yabe

et al. 2006

Biological & Pharmaceutical Bulletin

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“…For liver gene delivery, in addition to generating liverspecific liposomes by labeling them with asialoglycoprotein receptor ligands, such as asialofetuin or steylglucoside, 16,17 portal vein administration of lipoplexes has been shown to be a more effective approach than systemic administration. 4 The present study also showed that a one-log level increase (2.4 Â 10 4 versus 2.4 Â 10 3 RLU/mg protein) in luciferase activity was achieved when lipoplexes were administered via portal vein compared to tail vein injection.…”

Section: Liposome-mediated Liver Gene Deliverymentioning

confidence: 99%

Poly(cationic lipid)-mediated in vivo gene delivery to mouse liver

et al. 2003

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We have previously demonstrated that liposomes generated from poly(cationic lipid) (PCL) and cholesterol (Chol) have low cytotoxicity, are serum resistant, and display a transfection efficiency in vitro similar to commercially available cationic liposomes. Our in vivo experiments demonstrated that PCL-Chol liposomes bound much less avidly to serum proteins than did liposomes composed of 1,2-bis(dioleoyloxy)-3-(trimethylamonio)propane (DOTAP)-Chol or DO-TAP-L-a dioleoyl phosphatidylethanolamine (DOPE). Injection of the lipoplexes (PCL-Chol+DNA) through the portal vein after partial hepatectomy (PH) led to much higher reporter gene expression (luciferase) in the liver than did naked DNA injection. Marked green fluorescent protein expression was visualized in almost all hepatocytes in the liver of mice receiving lipoplex injection, even in the absence of PH. Subcutaneous injection of thyroid hormone triiodothyromine (T 3 ) significantly promoted hepatocyte regeneration and markedly enhanced PCL-Chol-mediated gene transfer in mouse liver when the lipoplex was administrated through either portal or tail vein. With T 3 pretreatment, PCL-Chol exerted a better gene transfer efficacy in mouse liver than DOTAP-Chol or DOTAP-DOPE. Two injections of lipoplexes through an indwelling catheter in the portal vein extended the transgene expression at a high level when T 3 injection was repeated. In conclusion, our findings demonstrate that the polymerized cationic liposomes are very stable in the blood and are effective agents for in vivo gene delivery, and that thyroid hormone administration offers a noninvasive approach to enhance liposome-mediated liver gene delivery.

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“…This method has proven to be a viable option for the clinical treatment of several diseases, including cystic fibrosis and cancer. 5,10,11 A second method used to enhance the specificity of gene therapy is by coupling cell-binding ligands, such as folic acid (FA), [12][13][14][15] transferrin 16 or carbohydrates 17 to liposomes for the purpose of combining the intrinsic activities of lipids with the receptor-mediated uptake properties of the applied ligand.…”

Section: Introductionmentioning

confidence: 99%

Folate-targeted, cationic liposome-mediated gene transfer into disseminated peritoneal tumors

Reddy

Abburi

Hofland³

et al. 2002

Gene Ther

161

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Liver-targeted gene transfer into a human hepatoblastoma cell line and in vivo by sterylglucoside-containing cationic liposomes

Cited by 40 publications

References 28 publications

Intracellular Trafficking Is the Important Process That Determines the Optimal Charge Ratio on Transfection by Galactosylated Lipoplex in HepG2 Cells

Intracellular Trafficking Is the Important Process That Determines the Optimal Charge Ratio on Transfection by Galactosylated Lipoplex in HepG2 Cells

Poly(cationic lipid)-mediated in vivo gene delivery to mouse liver

Folate-targeted, cationic liposome-mediated gene transfer into disseminated peritoneal tumors

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