Mannosylated chitosan-graft-polyethylenimine as a gene carrier for Raw 264.7 cell targeting.
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.
Jiang
Hu-Lin
HL
Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Republic of Korea.
Kim
You-Kyoung
YK
Arote
Rohidas
R
Jere
Dhananjay
D
Quan
Ji-Shan
JS
Yu
Jia-Hui
JH
Choi
Yun-Jaie
YJ
Nah
Jae-Woon
JW
Cho
Myung-Haing
MH
Cho
Chong-Su
CS
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
D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D011094:Polyethyleneimine; D048271:Chitosan; D008358:Mannose