Linear polyethyleneimine grafted to a hyperbranched poly(ethylene glycol)-like core: A copolymer for gene delivery

被引:44
作者
Banerjee, P [1 ]
Weissleder, R [1 ]
Bogdanov, A [1 ]
机构
[1] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA
关键词
D O I
10.1021/bc050083e
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
A block copolymer of a hyperbranched poly(ethylene glycol)-like core and linear polyethylenimine (HBP) was synthesized by a facile synthetic route that included (1) a single-step cationic copolymerization of diepoxy and polyhydroxyl monomers, (2) derivatization of hydroxyl groups of the core HBPEG copolymer with either tosyl or chloromethylbenzoyl chlorides resulting in a corresponding macroinitiator, and (3) synthesis of HBPEG-block-poly(alkyl oxazolines). HBPEG-block-linear polyethyleneimine (HBP) was obtained by hydrolysis of HBPEG-block-poly(alkyl oxazolines). Linear PEI-bearing hyperbranched polycations (HBP) had lower inherent toxicity in cell culture than PEG-grafted linear polyethyleneimines (PEGLPEI). PEGLPEI formed a complex with DNA with an average diameter of 250 nm. The complexes were loosely condensed and formed aggregates and precipitates during storage. By contrast, hyperbranched polycations (HBP) formed similar to 50 nm nanocomplexes with DNA that were stable for several weeks and showed resistance to DNAse I-mediated degradation. The 'inverted' block copolymers showed several orders of magnitude higher transfection efficiency than PEGLPEI in vitro. Because of the biocompatibility and higher transfection efficiency, the 'inverted' block copolymer merits further investigation as a gene carrier.
引用
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页码:125 / 131
页数:7
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