Increased liver uptake of liposomes and improved targeting efficacy by labeling with asialofetuin in rodents

Wu, Jian; Liu, Pei; Zhu, Jian Liang; Maddukuri, Sivaramaiah; Zern, Mark Α.

doi:10.1002/hep.510270319

Cited by 81 publications

(55 citation statements)

References 30 publications

(50 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…28 [ 3 H]-Cholesterol was added into the lipid mixture before hydration according to a method described previously. 28 The size distribution of three formulations of cationic liposomes before mixing with plasmid DNA was between 200 and 300 nm.…”

Section: Chemicalsmentioning

confidence: 99%

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

et al. 2003

View full text Add to dashboard Cite

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.

show abstract

Section: Chemicalsmentioning

confidence: 99%

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

et al. 2003

View full text Add to dashboard Cite

show abstract

“…1 Asialofetuin (AF), a glycoprotein having triantennary galactose terminal sugar chains, is known as an excellent ligand molecule selectively recognized by ASGPr. 2 For liver gene delivery, both virus-mediated [3][4][5] and non-viral systems have been considered. Although some of the virus-mediated gene transfer systems have been found to be quite effective, their usefulness is limited, given that they induce an immune response, leading to the rapid rejection of transduced cells.…”

Section: Introductionmentioning

confidence: 99%

Increased receptor-mediated gene delivery to the liver by protamine-enhanced-asialofetuin-lipoplexes

2003

View full text Add to dashboard Cite

A novel lipidic vector composed of DOTAP/Chol liposomes, asialofetuin (AF), protamine sulfate and DNA has been developed. The resulting protamine-AF-lipoplexes improved significantly the levels of gene expression in cultured cells and in the liver upon i.v. administration. Lipoplexes containing the optimal amount of AF (1 mg/mg DNA) showed a 16-fold higher transfection activity in HepG2 cells than nontargeted (plain) complexes. The uptake by cells having asialoglycoprotein receptors (ASGPr) on their plasma membrane was decreased by the addition of free AF, indicating that AF-lipoplexes were taken up specifically by cells via ASGPr-mediated endocytosis. Results from transfections performed in cells defective in ASGPr, ie HeLa cells, confirmed this mechanism. By addition of the condensing peptide, protamine sulfate, smaller complexes were obtained, which enhanced even more the uptake of AFcomplexes in HepG2 cells and in the liver. The optimal amount of protamine was 0.4 mg/mg DNA, and gene expression was about 5-fold over that obtained with AF-lipoplexes in the absence of the peptide, and 75-fold higher than that with plain conventional lipoplexes. Protamine-AF-lipoplexes increased by a factor of 12 luciferase gene expression in the liver of mice administered systemically via the tail vein, compared to plain complexes. In summary, our findings extend the scope of previous studies where AF-lipoplexes were used to introduce DNA into hepatocytes. The combination of targeting and protamine condensation obviated the need for partial hepatectomy, commonly required to obtain efficient gene delivery in this organ. Since protamine sulfate has been proven to be non-toxic in humans, the novel liverspecific vector described here may be useful for the delivery of clinically important genes to this organ.

show abstract

“…After intravenous administration, asialofetuin-modified liposomes were rapidly eliminated from the blood, and most were recovered from the liver [129]. Intrahepatic distribution studies revealed that asialofetuin-modified liposomes were selectively found in liver parenchymal cells [130] and Wu et al reported that asialofetuin-modified liposomes distributed in the liver in combination with intravenously injected vitamin E improved the protective effect against CCl4-induced acute liver injury in mice [130].…”

Section: Galactosylated Liposomesmentioning

confidence: 99%

Glycosylation-mediated targeting of carriers

Kawakami

Hashida

2014

Journal of Controlled Release

View full text Add to dashboard Cite

For safe and effective therapy, drugs should be delivered selectively to their target tissues or cells at an optimal rate. Drug delivery system technology maximizes the therapeutic efficacy and minimizes unfavorable drug actions by controlling their distribution profiles. Ligand-receptor binding is a typical example of specific recognition mechanisms in the body; therefore, ligand-modified drug carriers have been developed for active targeting based on receptor-mediated endocytosis. Among the various ligands reported thus far, sugar recognition is a promising approach for active targeting because of their high affinity and expression. Glycosylation has been applied for both macromolecular and liposomal carriers for cell-selective drug targeting.Recently, the combination of ultrasound exposure and glycosylated bubble liposomes has been developed. In this review, recent advances of glycosylation-mediated targeted drug delivery systems are discussed.

show abstract

Increased liver uptake of liposomes and improved targeting efficacy by labeling with asialofetuin in rodents

Cited by 81 publications

References 30 publications

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

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

Increased receptor-mediated gene delivery to the liver by protamine-enhanced-asialofetuin-lipoplexes

Glycosylation-mediated targeting of carriers

Contact Info

Product

Resources

About