Cationic star polymers consisting of alpha-cyclodextrin core and oligoethylenimine arms as nonviral gene delivery vectors.
A series of novel cationic star polymers were synthesized by conjugating multiple oligoethylenimine (OEI) arms onto an alpha-cyclodextrin (alpha-CD) core as nonviral gene delivery vectors. The molecular structures of the alpha-CD-OEI star polymers, which contained linear or branched OEI arms with different chain lengths ranging from 1 to 14 ethylenimine units, were characterized by using size exclusion chromatography, 13C and 1H NMR, and elemental analysis. The alpha-CD-OEI star polymers were studied in terms of their DNA binding capability, formation of nanoparticles with plasmid DNA (pDNA), cytotoxicity, and gene transfection in cultured cells. All the alpha-CD-OEI star polymers could inhibit the migration of pDNA on agarose gel through formation of complexes with pDNA, and the complexes formed nanoparticles with sizes ranging from 100 to 200 nm at N/P ratios of 8 or higher. The star polymers displayed much lower in vitro cytotoxicity than that of branched polyethylenimine (PEI) of molecular weight 25K. The alpha-CD-OEI star polymers showed excellent gene transfection efficiency in HEK293 and Cos7 cells. Generally, the transfection efficiency increased with an increase in the OEI arm length. The star polymers with longer and branched OEI arms showed higher transfection efficiency. The best one of the star polymers for gene delivery showed excellent in vitro transfection efficiency that was comparable to or even higher than that of branched PEI (25K). The novel alpha-CD-OEI star polymers with OEI arms of different chain lengths and chain architectures can be promising new nonviral gene delivery vectors with low cytotoxicity and high gene transfection efficiency for future gene therapy applications.
Yang
Chuan
C
Division of Bioengineering, Faculty of Engineering, National University of Singapore, 7 Engineering Drive 1, Singapore 117574, Singapore.
Li
Hongzhe
H
Goh
Suat Hong
SH
Li
Jun
J
D000818:Animals; D019556:COS Cells; D002412:Cations / Q000737:chemistry; D002460:Cell Line; D002522:Chlorocebus aethiops; D002850:Chromatography, Gel; D004247:DNA / Q000378:metabolism; D004577:Electron Probe Microanalysis; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000737:chemistry*; D006801:Humans; D008027:Light; D008156:Luciferases / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D018613:Microscopy, Confocal; D015394:Molecular Structure; D008970:Molecular Weight; D053758:Nanoparticles; D010316:Particle Size; D010957:Plasmids / Q000378:metabolism; D011094:Polyethyleneimine / Q000737:chemistry / Q000378:metabolism; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D012542:Scattering, Radiation; D014162:Transfection; D047391:alpha-Cyclodextrins / Q000737:chemistry / Q000378:metabolism
D002412:Cations; D011108:Polymers; D047391:alpha-Cyclodextrins; D011094:Polyethyleneimine; D004247:DNA; D008156:Luciferases; C032613:alpha-cyclodextrin