title: The biocompatibility of fatty acid modified dextran-agmatine bioconjugate gene delivery vector.
abstract: 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-Agm and Dex-L-Agm were assessed in detail by hemolytic activity determination, red blood cell aggregation assay as well as MTT evaluation of degraded products. Dex-Agm and Dex-L-Agm were shown to be highly cytocompatible without causing hemolysis and red blood cell aggregation presumably owing to the bidentate hydrogen bonding of guanidine with the constituents present in cell membrane rather than electrostatic interactions alone which could cause cell damage. Importantly, cells cultured with the degraded products of Dex-Agm and Dex-L-Agm retained more than 80% viability, suggest their potential application as a gene delivery vector.
authors: School of Materials Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin 30072, PR China.
authors: Jianhai
authors: J
authors: Yang
authors: Yuan
authors: Y
authors: Liu
authors: Hongbo
authors: H
authors: Wang
authors: Lu
authors: L
authors: Liu
authors: Wei
authors: W
authors: Wang
authors: Chuandong
authors: C
authors: Wang
authors: Qin
authors: Q
authors: Wang
authors: Wenguang
authors: W
authors: Liu
mesh_terms: D000376:Agmatine / Q000737:chemistry*; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D019556:COS Cells; D002470:Cell Survival; D002522:Chlorocebus aethiops; D004247:DNA / Q000378:metabolism; D003911:Dextrans / Q000737:chemistry*; D004912:Erythrocytes / Q000737:chemistry; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000737:chemistry*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007850:Lauric Acids / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D014162:Transfection / Q000379:methods*
chemical_list: D001672:Biocompatible Materials; D003911:Dextrans; D007850:Lauric Acids; C030358:lauric acid; D049452:Green Fluorescent Proteins; D000376:Agmatine; D004247:DNA; D008156:Luciferases