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A lauric acid modified dextran-agmatine bioconjugate (Dex-l-Agm) was prepared by 1,1′-carbonyldiimidazole (CDI) activation and the nucleophilic reaction between tosyl of tosylated dextran and primary amine of agmatine. Dextran-agmatine bioconjugates (Dex-Agm) were capable of condensing DNA into nanocomplexes, and combining lauric acid promoted the complexation with DNA supposedly due to the cooperative binding effect attributed to hydrophobic interaction. Higher degree substitution of agmatine and hydrophobic grafting resulted in increased luciferase activities expressed in COS-7 and HEK293 cells; Semiquantitative assay of GFP expression by flow cytometry in COS-7, HEK293 and CHOK1 cells further demonstrated that conjugation of fatty acid could remarkably increase gene transfection of Dex-Agm in spite of 1.1–2.3-fold lower efficiency compared to Exgen 500. The biocompatibilities of Dex …