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, similar to2 mumol/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 similar to2 mumol/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.
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