N-Succinyl-chitosan grafted with low molecular weight polyethylenimine as a serum-resistant gene vector.
Low transfection efficiency and inactivation by serum are the major drawbacks for cationic polymers when used as non-viral gene vectors. Here, a series of N-succinyl-chitosan-graft-polyethylenimine (NSC-g-PEI) copolymers with different compositions were synthesized through grafting low molecular weight PEI (800 Da) to N-succinyl-chitosan. An agarose gel electrophoresis assay showed NSC-g-PEIs had good binding capability with DNA and the particle size of the NSC-g-PEI-DNA complexes was between 150 to 300 nm as determined by a Zeta sizer. In vitro transfection of NSC-g-PEI-DNA complexes for 293T, HeLa and CHO cells was investigated. It was found that the transfection efficiency of NSC-g-PEI-DNA complexes was higher than that of DNA combined PEI (25 kDa) and the transfection efficiency increased with the increasing GD of PEI. More importantly, the NSC-g-PEI-DNA complexes were stable and the transfection efficiency was not affected obviously in the presence of serum with different concentrations. In addition, NSC-g-PEIs had a lower cytotoxicity than PEI (25 kDa) and the toxicity increased with increasing GD of PEI. The NSC-g-PEI copolymers will have a good potential as efficient non-viral gene vectors in the presence of serum.
Lu
Bo
B
Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan, P. R. China.
Sun
Yun-Xia
YX
Li
Yun-Qiu
YQ
Zhang
Xian-Zheng
XZ
Zhuo
Ren-Xi
RX
D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D006224:Cricetinae; D003412:Cricetulus; D003470:Culture Media / Q000494:pharmacology; D004247:DNA / Q000737:chemistry / Q000235:genetics* / Q000648:ultrastructure; D004587:Electrophoresis, Agar Gel; D006367:HeLa Cells; D006801:Humans; D046911:Macromolecular Substances / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D008970:Molecular Weight; D010316:Particle Size; D011094:Polyethyleneimine / Q000737:chemistry*; D015203:Reproducibility of Results; D044967:Serum; D014162:Transfection / Q000379:methods*
D003470:Culture Media; D046911:Macromolecular Substances; C118639:N-succinyl-chitosan; D011094:Polyethyleneimine; D004247:DNA; D048271:Chitosan