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Cationic lipid polymerization as a novel approach for constructing new DNA delivery agents

Standard

Cationic lipid polymerization as a novel approach for constructing new DNA delivery agents. / Wu, J; Lizarzaburu, M E; Kurth, M J; Liu, L; Wege, H; Zern, M A; Nantz, M H.

in: BIOCONJUGATE CHEM, Jahrgang 12, Nr. 2, 2001, S. 251-7.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Wu, J, Lizarzaburu, ME, Kurth, MJ, Liu, L, Wege, H, Zern, MA & Nantz, MH 2001, 'Cationic lipid polymerization as a novel approach for constructing new DNA delivery agents', BIOCONJUGATE CHEM, Jg. 12, Nr. 2, S. 251-7.

APA

Wu, J., Lizarzaburu, M. E., Kurth, M. J., Liu, L., Wege, H., Zern, M. A., & Nantz, M. H. (2001). Cationic lipid polymerization as a novel approach for constructing new DNA delivery agents. BIOCONJUGATE CHEM, 12(2), 251-7.

Vancouver

Wu J, Lizarzaburu ME, Kurth MJ, Liu L, Wege H, Zern MA et al. Cationic lipid polymerization as a novel approach for constructing new DNA delivery agents. BIOCONJUGATE CHEM. 2001;12(2):251-7.

Bibtex

@article{4be88a88325a4fdaa2733c7472dfacca,
title = "Cationic lipid polymerization as a novel approach for constructing new DNA delivery agents",
abstract = "In vivo gene delivery mediated by cationic lipids is often compromised by aggregation due to complexation with proteins in the blood. To improve the stability of cationic lipid-DNA complexes, the present study aimed to develop a novel approach in which a poly(cationic lipid) (PCL) is utilized to form stable cationic polyplexes for gene transfection. Hydrogenation of the acrylamide analogue of betaAE-DMRI, the polymerizable precursor of PCL, provided a monomeric lipid derivative (MHL) which was used for direct comparison of corresponding lipoplex stability, toxicity, and transfection activity. Various formulations of cationic liposomes, such as MHL, MHL-cholesterol (Chol), PCL, PCL-Chol, DOTAP-Chol, and commercially available lipofectamine were generated and examined in this study. The new poly(cationic lipid) did not display any significant toxicity to rat hepatocytes or Hep G2 cells as indicated by an LDH leakage assay. Furthermore, PCL was significantly less toxic than MHL, DOTAP-Chol or lipofectamine. Suspensions of PCL were resistant to aggregation even after 24 h of exposure to solutions containing 50 and 100% fetal bovine serum (FBS). In contrast, suspensions of lipofectamine extensively aggregated after 24 h of exposure to 50% FBS. To examine the influence of lipid polymerization on gene transfer activity, liposome-mediated transfections of a luciferase vector (pGL3) were performed in Hep G2 and Alexander cell lines. The luciferase activity of the PCL formulations in Hep G2 cells were similar to those of the MHL, DOTAP-Chol and lipofectamine formulations, demonstrating that lipid polymerization does not compromise transfection activity. In comparison to the monomeric precursor MHL and to the industry transfection standards DOTAP and lipofectamine, the novel poly(cationic lipid) exhibited the lowest cytotoxicity, was the most resistant to serum-induced aggregation and had comparable transfection activity when coformulated with cholesterol. This novel polymerization approach for the development of stable and active polyplexes may prove a valuable alternative for in vivo gene delivery.",
keywords = "Animals, Cation Exchange Resins, Cell Line, Cholesterol, Drug Carriers, Fatty Acids, Monounsaturated, Fluorescent Dyes, Gene Transfer Techniques, Hepatocytes, Humans, Indicators and Reagents, Lipids, Liposomes, Molecular Structure, Particle Size, Polyamines, Quaternary Ammonium Compounds, Rats, Rats, Sprague-Dawley, Transfection",
author = "J Wu and Lizarzaburu, {M E} and Kurth, {M J} and L Liu and H Wege and Zern, {M A} and Nantz, {M H}",
year = "2001",
language = "English",
volume = "12",
pages = "251--7",
journal = "BIOCONJUGATE CHEM",
issn = "1043-1802",
publisher = "American Chemical Society",
number = "2",

}

RIS

TY - JOUR

T1 - Cationic lipid polymerization as a novel approach for constructing new DNA delivery agents

AU - Wu, J

AU - Lizarzaburu, M E

AU - Kurth, M J

AU - Liu, L

AU - Wege, H

AU - Zern, M A

AU - Nantz, M H

PY - 2001

Y1 - 2001

N2 - In vivo gene delivery mediated by cationic lipids is often compromised by aggregation due to complexation with proteins in the blood. To improve the stability of cationic lipid-DNA complexes, the present study aimed to develop a novel approach in which a poly(cationic lipid) (PCL) is utilized to form stable cationic polyplexes for gene transfection. Hydrogenation of the acrylamide analogue of betaAE-DMRI, the polymerizable precursor of PCL, provided a monomeric lipid derivative (MHL) which was used for direct comparison of corresponding lipoplex stability, toxicity, and transfection activity. Various formulations of cationic liposomes, such as MHL, MHL-cholesterol (Chol), PCL, PCL-Chol, DOTAP-Chol, and commercially available lipofectamine were generated and examined in this study. The new poly(cationic lipid) did not display any significant toxicity to rat hepatocytes or Hep G2 cells as indicated by an LDH leakage assay. Furthermore, PCL was significantly less toxic than MHL, DOTAP-Chol or lipofectamine. Suspensions of PCL were resistant to aggregation even after 24 h of exposure to solutions containing 50 and 100% fetal bovine serum (FBS). In contrast, suspensions of lipofectamine extensively aggregated after 24 h of exposure to 50% FBS. To examine the influence of lipid polymerization on gene transfer activity, liposome-mediated transfections of a luciferase vector (pGL3) were performed in Hep G2 and Alexander cell lines. The luciferase activity of the PCL formulations in Hep G2 cells were similar to those of the MHL, DOTAP-Chol and lipofectamine formulations, demonstrating that lipid polymerization does not compromise transfection activity. In comparison to the monomeric precursor MHL and to the industry transfection standards DOTAP and lipofectamine, the novel poly(cationic lipid) exhibited the lowest cytotoxicity, was the most resistant to serum-induced aggregation and had comparable transfection activity when coformulated with cholesterol. This novel polymerization approach for the development of stable and active polyplexes may prove a valuable alternative for in vivo gene delivery.

AB - In vivo gene delivery mediated by cationic lipids is often compromised by aggregation due to complexation with proteins in the blood. To improve the stability of cationic lipid-DNA complexes, the present study aimed to develop a novel approach in which a poly(cationic lipid) (PCL) is utilized to form stable cationic polyplexes for gene transfection. Hydrogenation of the acrylamide analogue of betaAE-DMRI, the polymerizable precursor of PCL, provided a monomeric lipid derivative (MHL) which was used for direct comparison of corresponding lipoplex stability, toxicity, and transfection activity. Various formulations of cationic liposomes, such as MHL, MHL-cholesterol (Chol), PCL, PCL-Chol, DOTAP-Chol, and commercially available lipofectamine were generated and examined in this study. The new poly(cationic lipid) did not display any significant toxicity to rat hepatocytes or Hep G2 cells as indicated by an LDH leakage assay. Furthermore, PCL was significantly less toxic than MHL, DOTAP-Chol or lipofectamine. Suspensions of PCL were resistant to aggregation even after 24 h of exposure to solutions containing 50 and 100% fetal bovine serum (FBS). In contrast, suspensions of lipofectamine extensively aggregated after 24 h of exposure to 50% FBS. To examine the influence of lipid polymerization on gene transfer activity, liposome-mediated transfections of a luciferase vector (pGL3) were performed in Hep G2 and Alexander cell lines. The luciferase activity of the PCL formulations in Hep G2 cells were similar to those of the MHL, DOTAP-Chol and lipofectamine formulations, demonstrating that lipid polymerization does not compromise transfection activity. In comparison to the monomeric precursor MHL and to the industry transfection standards DOTAP and lipofectamine, the novel poly(cationic lipid) exhibited the lowest cytotoxicity, was the most resistant to serum-induced aggregation and had comparable transfection activity when coformulated with cholesterol. This novel polymerization approach for the development of stable and active polyplexes may prove a valuable alternative for in vivo gene delivery.

KW - Animals

KW - Cation Exchange Resins

KW - Cell Line

KW - Cholesterol

KW - Drug Carriers

KW - Fatty Acids, Monounsaturated

KW - Fluorescent Dyes

KW - Gene Transfer Techniques

KW - Hepatocytes

KW - Humans

KW - Indicators and Reagents

KW - Lipids

KW - Liposomes

KW - Molecular Structure

KW - Particle Size

KW - Polyamines

KW - Quaternary Ammonium Compounds

KW - Rats

KW - Rats, Sprague-Dawley

KW - Transfection

M3 - SCORING: Journal article

C2 - 11312686

VL - 12

SP - 251

EP - 257

JO - BIOCONJUGATE CHEM

JF - BIOCONJUGATE CHEM

SN - 1043-1802

IS - 2

ER -