Amino Acid-Substituted Dextran-Based Non-Viral Vectors for Gene Delivery

To form bio-inspired non-viral vectors for DNA delivery, the polysaccharide dextran is allowed to react with Boc-amino protected amino acids glycine, beta-alanine, and L-lysine activated with 1,1'-carbonyldiimidazole and subsequent dextran ester deprotection. A library of such dextran esters is made available to investigate the relationship between polymer structure, complex formation, stability, toxicity, and transfection. Only dextran esters of beta-alanine and L-lysine are able to efficiently interact with DNA as shown by dye exclusion assays, to form nanosized complexes (70-110 nm) with positive zeta potential. With increasing substitution degree and complex charge ratios, the L-lysine esters accomplish more effective binding and protection of DNA against enzymatic degradation than beta-alanine esters. However, luciferase reporter gene assays reveal higher transfection for beta-alanine than for L-lysine esters due to a more effective DNA release and better suited buffing area of the amino groups triggering the endosomal release. Conclusively, beta-alanine-substituted dextran derivatives may serve as promising non-viral vectors.