N-Acetylglucosamine-conjugated block copolymer consisting of poly(ethylene oxide) and cationic polyaspartamide as a gene carrier for targeting vimentin-expressing cells.
Gene therapy is not successful due to lack of safe gene delivery vector, low transfection efficiency and inability to target the particular cells. Here, we synthesized a biocompatible block copolymer (abbreviated as PASPG) which consists of cationic poly[(aspartamide)(spermine)] for complexation with DNA and enhancing transfection efficiency due to buffering ability of spermine, poly(ethylene oxide)(PEO) for stability after systemic administration of the gene and N-acetylglucosamine (GlcNAc) as a specific ligand to target vimentin-expressing cells. Primarily, PASPG showed efficient complexation with DNA. Cell viability assay demonstrated that PASPG had low toxicity compared to polyethylenimine 25K. Furthermore, PASPG showed higher transfection efficiency in vimentin-expressing cells than vimentin-deficient ones due to the recognition of GlcNAc in the polymeric gene carrier by vimentin in the cells for the receptor-mediated endocytosis of PASPG. Favorably, the serum had no effect on transfection efficiency of PASPG due to the presence of hydrophilic PEO in the block copolymer. This study reveals that GlcNAc-coupled biocompatible block copolymer can specifically deliver gene to vimentin-expressing cells.
Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, South Korea; Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, South Korea; Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
You-Kyoung
YK
Kim
Bijay
B
Singh
Hu-Lin
HL
Jiang
Tae-Eun
TE
Park
Tao
T
Jiang
In-Kyu
IK
Park
Myung-Haing
MH
Cho
Sang-Kee
SK
Kang
Yun-Jaie
YJ
Choi
Chong-Su
CS
Cho
D000117:Acetylglucosamine / Q000235:genetics*; D002412:Cations / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004247:DNA / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000737:chemistry* / Q000235:genetics; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D013096:Spermine / Q000737:chemistry; D014162:Transfection / Q000379:methods; D014746:Vimentin / Q000235:genetics*
D002412:Cations; D011108:Polymers; D014746:Vimentin; D013096:Spermine; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D004247:DNA; D000117:Acetylglucosamine
Block copolymer; Gene delivery; Kidney fibrosis; N-acetylglucosamine; Vimentin