General structure-activity relationship for poly(glycoamidoamine)s: the effect of amine density on cytotoxicity and DNA delivery efficiency

Bioconjugate Chemistry
Chen-Chang LeeTheresa M Reineke

Abstract

Herein, two new series of poly(glycoamidoamine)s (branched and linear) have been synthesized by polycondensation. The polymer repeat units have been designed to contain D-glucaramide, meso-galactaramide, D-mannaramide, or L-tartaramide structures and five or six ethyleneamine units to investigate the amine density effects on the bioactivity as compared to a similar series of poly(glycoamidoamine)s previously described that contain four ethyleneamines. These delivery vehicles were created to examine the effects that the number of secondary amines in the polymer repeat unit and the polymer structure (branched and linear) have on plasmid DNA (pDNA) binding affinity, polyplex formation, cell viability, and gene expression in the absence and presence of serum in the culture medium. The results reveal that the new polymers with higher amine density in the repeat unit do not significantly enhance the transfection efficiency compared to that of previous models containing four ethyleneamines, but an increase in cytotoxicity is noticed. Linear polymers reveal higher pDNA neutralization efficacy, gene expression, and toxicity than the branched versions containing a similar chemical structure, which may be caused by a higher protonation of...Continue Reading

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Citations

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