Galactosyl conjugated N-succinyl-chitosan-graft-polyethylenimine for targeting gene transfer.
Through incorporating lactobionic acid (LA) bearing a galactose group to N-succinyl-chitosan-graft-polyethylenimine (NSC-g-PEI), NSC-g-PEI-LA copolymers were synthesized as gene vectors with hepatocyte targeting properties. The molecular weight and composition of NSC-g-PEI-LA copolymers were characterized using gel permeation chromatography (GPC) and (1)H nuclear magnetic resonance spectroscopy ((1)H NMR) respectively. Agarose gel electrophoresis assays showed good DNA binding ability of NSC-g-PEI-LA, and the particle size of the NSC-g-PEI-LA/DNA complexes were between 150 and 400 nm as determined by a Zeta sizer. The NSC-g-PEI-LA/DNA complexes observed by scanning electron microscopy (SEM) exhibited a compact and spherical morphology. The zeta potentials of these complexes were increased with the weight ratio of NSC-g-PEI-LA/DNA. NSC-g-PEI-LA has a lower cytotoxicity than PEI (25 kDa) and the toxicity decreased with increasing substitution of LA. The transfection efficiency of different complexes was evaluated by luciferase assay. Compared with PEI (25 kDa) and NSC-g-PEI/DNA, NSC-g-PEI-LA showed good transfection activity and cell specificity to HepG2 cells. The results suggested that NSC-g-PEI-LA has the potential to be used as a safe and effective targeting gene vector.
Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, P. R. China.
Bo
B
Lu
De-Qun
DQ
Wu
Hua
H
Zheng
Chang-Yun
CY
Quan
Xian-Zheng
XZ
Zhang
Ren-Xi
RX
Zhuo
D002021:Buffers; D002460:Cell Line; D002470:Cell Survival; D048271:Chitosan / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D004247:DNA / Q000378:metabolism; D004187:Disaccharides / Q000737:chemistry; D004587:Electrophoresis, Agar Gel; D005690:Galactose / Q000737:chemistry*; D018014:Gene Transfer Techniques; D006801:Humans; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D011094:Polyethyleneimine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*; D017186:Titrimetry; D014162:Transfection
D002021:Buffers; D004187:Disaccharides; C005608:lactobionic acid; D011094:Polyethyleneimine; D004247:DNA; D048271:Chitosan; D005690:Galactose