Cationic polysaccharides for gene delivery

Tony Azzam, Arthur Raskin, Arik Makovitzki, Henry Brem, Pierre Vierling, Michal Lineal, Abraham J. Domb

Research output: Contribution to journalArticle

Abstract

Cationic polysaccharides based on spermine-dextran conjugates were synthesized and tested as vectors for gene transfection. Dextrans of 10-380 kDa were oxidized under mild conditions by potassium periodate to obtain the respective polyaldehydes in 90% overall yield. The oxidized dextrans were reacted by reductive amination with increasing amounts of spermine, and the efficacy of conjugation between the oligoamine and polysaccharides was studied as a function of spermine/aldehyde mole ratio, pH, and temperature of medium. The optimal conjugation yields were obtained at 1.25 mole ratio (spermine/aldehyde groups) and pH 11 at room temperature. Under these conditions, ∼2 μmol/mg (spermine/polysaccharide) conjugation was achieved with 25-30% of the spermine moieties were conjugated in both sides to form branched polymers. The water-soluble polymers obtained were interacted with pCMV-GFP plasmid to form nanoparticles that were introduced to HEK293 and NIH3T3 cells in vitro for transfection efficacy assessment. Out of about 50 different polymer structures, only spermine-dextran of 6000-8000 Da, spermine content of ∼2 ∼mol/mg, and degree of branching of 25-30% was active in transfecting about 50% of the cells while all other polymers were significantly less active.

Original languageEnglish (US)
Pages (from-to)9947-9953
Number of pages7
JournalMacromolecules
Volume35
Issue number27
DOIs
StatePublished - Dec 31 2002

Fingerprint

Spermine
Dextran
Polysaccharides
Genes
Polymers
Dextrans
Aldehydes
Amination
Potassium
Nanoparticles
Temperature
Water
Plasmids

ASJC Scopus subject areas

  • Materials Chemistry

Cite this

Azzam, T., Raskin, A., Makovitzki, A., Brem, H., Vierling, P., Lineal, M., & Domb, A. J. (2002). Cationic polysaccharides for gene delivery. Macromolecules, 35(27), 9947-9953. https://doi.org/10.1021/ma0209592

Cationic polysaccharides for gene delivery. / Azzam, Tony; Raskin, Arthur; Makovitzki, Arik; Brem, Henry; Vierling, Pierre; Lineal, Michal; Domb, Abraham J.

In: Macromolecules, Vol. 35, No. 27, 31.12.2002, p. 9947-9953.

Research output: Contribution to journalArticle

Azzam, T, Raskin, A, Makovitzki, A, Brem, H, Vierling, P, Lineal, M & Domb, AJ 2002, 'Cationic polysaccharides for gene delivery', Macromolecules, vol. 35, no. 27, pp. 9947-9953. https://doi.org/10.1021/ma0209592
Azzam T, Raskin A, Makovitzki A, Brem H, Vierling P, Lineal M et al. Cationic polysaccharides for gene delivery. Macromolecules. 2002 Dec 31;35(27):9947-9953. https://doi.org/10.1021/ma0209592
Azzam, Tony ; Raskin, Arthur ; Makovitzki, Arik ; Brem, Henry ; Vierling, Pierre ; Lineal, Michal ; Domb, Abraham J. / Cationic polysaccharides for gene delivery. In: Macromolecules. 2002 ; Vol. 35, No. 27. pp. 9947-9953.
@article{8cc79f5b0b9749fca72b4b579a571ec2,
title = "Cationic polysaccharides for gene delivery",
abstract = "Cationic polysaccharides based on spermine-dextran conjugates were synthesized and tested as vectors for gene transfection. Dextrans of 10-380 kDa were oxidized under mild conditions by potassium periodate to obtain the respective polyaldehydes in 90{\%} overall yield. The oxidized dextrans were reacted by reductive amination with increasing amounts of spermine, and the efficacy of conjugation between the oligoamine and polysaccharides was studied as a function of spermine/aldehyde mole ratio, pH, and temperature of medium. The optimal conjugation yields were obtained at 1.25 mole ratio (spermine/aldehyde groups) and pH 11 at room temperature. Under these conditions, ∼2 μmol/mg (spermine/polysaccharide) conjugation was achieved with 25-30{\%} of the spermine moieties were conjugated in both sides to form branched polymers. The water-soluble polymers obtained were interacted with pCMV-GFP plasmid to form nanoparticles that were introduced to HEK293 and NIH3T3 cells in vitro for transfection efficacy assessment. Out of about 50 different polymer structures, only spermine-dextran of 6000-8000 Da, spermine content of ∼2 ∼mol/mg, and degree of branching of 25-30{\%} was active in transfecting about 50{\%} of the cells while all other polymers were significantly less active.",
author = "Tony Azzam and Arthur Raskin and Arik Makovitzki and Henry Brem and Pierre Vierling and Michal Lineal and Domb, {Abraham J.}",
year = "2002",
month = "12",
day = "31",
doi = "10.1021/ma0209592",
language = "English (US)",
volume = "35",
pages = "9947--9953",
journal = "Macromolecules",
issn = "0024-9297",
publisher = "American Chemical Society",
number = "27",

}

TY - JOUR

T1 - Cationic polysaccharides for gene delivery

AU - Azzam, Tony

AU - Raskin, Arthur

AU - Makovitzki, Arik

AU - Brem, Henry

AU - Vierling, Pierre

AU - Lineal, Michal

AU - Domb, Abraham J.

PY - 2002/12/31

Y1 - 2002/12/31

N2 - Cationic polysaccharides based on spermine-dextran conjugates were synthesized and tested as vectors for gene transfection. Dextrans of 10-380 kDa were oxidized under mild conditions by potassium periodate to obtain the respective polyaldehydes in 90% overall yield. The oxidized dextrans were reacted by reductive amination with increasing amounts of spermine, and the efficacy of conjugation between the oligoamine and polysaccharides was studied as a function of spermine/aldehyde mole ratio, pH, and temperature of medium. The optimal conjugation yields were obtained at 1.25 mole ratio (spermine/aldehyde groups) and pH 11 at room temperature. Under these conditions, ∼2 μmol/mg (spermine/polysaccharide) conjugation was achieved with 25-30% of the spermine moieties were conjugated in both sides to form branched polymers. The water-soluble polymers obtained were interacted with pCMV-GFP plasmid to form nanoparticles that were introduced to HEK293 and NIH3T3 cells in vitro for transfection efficacy assessment. Out of about 50 different polymer structures, only spermine-dextran of 6000-8000 Da, spermine content of ∼2 ∼mol/mg, and degree of branching of 25-30% was active in transfecting about 50% of the cells while all other polymers were significantly less active.

AB - Cationic polysaccharides based on spermine-dextran conjugates were synthesized and tested as vectors for gene transfection. Dextrans of 10-380 kDa were oxidized under mild conditions by potassium periodate to obtain the respective polyaldehydes in 90% overall yield. The oxidized dextrans were reacted by reductive amination with increasing amounts of spermine, and the efficacy of conjugation between the oligoamine and polysaccharides was studied as a function of spermine/aldehyde mole ratio, pH, and temperature of medium. The optimal conjugation yields were obtained at 1.25 mole ratio (spermine/aldehyde groups) and pH 11 at room temperature. Under these conditions, ∼2 μmol/mg (spermine/polysaccharide) conjugation was achieved with 25-30% of the spermine moieties were conjugated in both sides to form branched polymers. The water-soluble polymers obtained were interacted with pCMV-GFP plasmid to form nanoparticles that were introduced to HEK293 and NIH3T3 cells in vitro for transfection efficacy assessment. Out of about 50 different polymer structures, only spermine-dextran of 6000-8000 Da, spermine content of ∼2 ∼mol/mg, and degree of branching of 25-30% was active in transfecting about 50% of the cells while all other polymers were significantly less active.

UR - http://www.scopus.com/inward/record.url?scp=0037207156&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037207156&partnerID=8YFLogxK

U2 - 10.1021/ma0209592

DO - 10.1021/ma0209592

M3 - Article

AN - SCOPUS:0037207156

VL - 35

SP - 9947

EP - 9953

JO - Macromolecules

JF - Macromolecules

SN - 0024-9297

IS - 27

ER -