title: Mannosylated chitosan-graft-polyethylenimine as a gene carrier for Raw 264.7 cell targeting.
abstract: Gene transfer using non-viral vectors is a promising approach for the safe delivery of therapeutic genes. Among non-viral vectors, chitosans have been proposed as alternative, biocompatible cationic polymers for non-viral gene delivery. However, the low transfection efficiency and low specificity of chitosan needs to be addressed prior to clinical application. In this study, mannosylated chitosan-graft-polyethylenimine (Man-CHI-g-PEI) copolymer was prepared by thiourea reaction between the isothiocyanate group of mannopyranosylphenylisothiocyanate and the amine groups of chitosan-graft-PEI (CHI-g-PEI) for targeting into antigen presenting cells (APCs) having mannose receptors. The composition and molecular weight were characterized using (1)H NMR and GPC, respectively. The copolymer was complexed with plasmid DNA in various copolymer/DNA (N/P) charge ratios, and the complexes were characterized. Man-CHI-g-PEI showed good DNA binding ability and high protection of DNA from nuclease attack and had low cytotoxicity compared with PEI 25K. The transfection efficiency of Man-CHI-g-PEI/DNA complexes into the Raw 264.7 macrophage cell line, which has mannose receptors, was higher than CHI-g-PEI itself as well as PEI 25K, indicating Man-CHI-g-PEI can be used as an APCs' targeting gene delivery carrier.
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: Hu-Lin
authors.initials: HL
authors.lastname: Jiang
authors.forename: You-Kyoung
authors.initials: YK
authors.lastname: Kim
authors.forename: Rohidas
authors.initials: R
authors.lastname: Arote
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Jere
authors.forename: Ji-Shan
authors.initials: JS
authors.lastname: Quan
authors.forename: Jia-Hui
authors.initials: JH
authors.lastname: Yu
authors.forename: Yun-Jaie
authors.initials: YJ
authors.lastname: Choi
authors.forename: Jae-Woon
authors.initials: JW
authors.lastname: Nah
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
authors.forename: Chong-Su
authors.initials: CS
authors.lastname: Cho
mesh_terms: D000818:Animals; D002460:Cell Line; D048271:Chitosan / Q000009:adverse effects / Q000737:chemistry*; D018390:Gene Targeting / Q000379:methods*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000009:adverse effects / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008358:Mannose / Q000737:chemistry; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D051379:Mice; D008970:Molecular Weight; D011094:Polyethyleneimine / Q000009:adverse effects / Q000737:chemistry*; D011956:Receptors, Cell Surface / Q000378:metabolism; D018675:Toxicity Tests; D014162:Transfection / Q000379:methods
chemical_list: D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D011094:Polyethyleneimine; D048271:Chitosan; D008358:Mannose