title: Poly(ethylene glycol)-block-polyethylenimine copolymers as carriers for gene delivery: effects of PEG molecular weight and PEGylation degree.
abstract: An ideal gene carrier is required both in safety and efficiency for transfection. Polyethylenimine (PEI), a well-studied cationic polymer, has been proved with high transfection efficiency, but is reported as toxicity in many cell lines. In this study, PEI was coupled with polyethylene glycol (PEG) to reduce its cytotoxicity. PEG-PEI copolymers were synthesized with isoporon diisocyanate (IPDI) in two steps. A set of PEG-PEI with different PEG molecular weights (MWs) and amounts of PEG were synthesized. The molecular structure of the resulting copolymers was evaluated by nuclear magnetic resonance spectroscopy ((1)H NMR), infrared spectroscopy (IR), and gel permeation chromatography (GPC), all of which had successfully verified formation of the copolymers. The particle size and zeta potential of polymer/DNA complexes were measured, and their cytotoxicity and transfection efficiency in Hela cells were evaluated. We found that the copolymer block structure significantly influenced not only the physicochemical properties of complexes, but also their cytotoxicity and transfection efficiency. PEG (5 kDa) significantly reduced the diameter of the spherical complexes. The zeta potential of complexes was reduced with increasing amount of PEG grafting. Cytotoxicity was dependent not on PEG MW but on the amount of PEG grafting. Copolymer PEG-PEI (2-25-1) with 1.89 PEG (2 kDa) was proved to be more efficient for in vitro gene transfer. In conclusion, PEG MW and the degree of PEGylation were found to significantly influence the biological activity of PEG-PEI/DNA complexes. These results provide new sights into the studies using block copolymer as gene delivery systems.
authors.affiliation: The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Shi-Rong
authors.initials: SR
authors.lastname: Pan
authors.forename: Hai-Mei
authors.initials: HM
authors.lastname: Hu
authors.forename: Gui-Fu
authors.initials: GF
authors.lastname: Wu
authors.forename: Min
authors.initials: M
authors.lastname: Feng
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Luo
mesh_terms: D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000138:chemical synthesis / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D008970:Molecular Weight; D011092:Polyethylene Glycols / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry; D013055:Spectrophotometry, Infrared
chemical_list: D011092:Polyethylene Glycols; D011094:Polyethyleneimine