Poly(ethylene glycol)-block-polyethylenimine copolymers as carriers for gene delivery: effects of PEG molecular weight and PEGylation degree.

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.

Zhang X ，Pan SR ，Hu HM ，Wu GF ，Feng M ，Zhang W ，Luo X ... -  《-》

Low molecular weight linear polyethylenimine-b-poly(ethylene glycol)-b-polyethylenimine triblock copolymers: synthesis, characterization, and in vitro gene transfer properties.

Zhong Z ，Feijen J ，Lok MC ，Hennink WE ，Christensen LV ，Yockman JW ，Kim YH ，Kim SW ... -  《BIOMACROMOLECULES》

Degradable polyethylenimine-alt-poly(ethylene glycol) copolymers as novel gene carriers.

Park MR ，Han KO ，Han IK ，Cho MH ，Nah JW ，Choi YJ ，Cho CS ... -  《JOURNAL OF CONTROLLED RELEASE》

Physicochemical and biological characterization of polyethylenimine-graft-poly(ethylene glycol) block copolymers as a delivery system for oligonucleotides and ribozymes.

Brus C ，Petersen H ，Aigner A ，Czubayko F ，Kissel T ... -  《BIOCONJUGATE CHEMISTRY》

PEG- and PDMAEG-graft-modified branched PEI as novel gene vector: synthesis, characterization and gene transfection.

Wen Y ，Pan S ，Luo X ，Zhang W ，Shen Y ，Feng M ... -  《-》