Polycationic block copolymers of poly(ethylene oxide) and poly(propylene oxide) for cell transfection

被引:43
|
作者
Bromberg, L
Deshmukh, S
Temchenko, M
Iourtchenko, L
Alakhov, V
Alvarez-Lorenzo, C
Barreiro-Iglesias, R
Concheiro, A
Hatton, TA [1 ]
机构
[1] MIT, Dept Chem Engn, Cambridge, MA 02139 USA
[2] Supratek Pharma Inc, Laval, PQ H7V 1B7, Canada
[3] Univ Santiago de Compostela, Fac Farm, Dept Farm & Tecnol Farmaceut, Santiago De Compostela 15872, Spain
关键词
D O I
10.1021/bc049749f
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
A facile, one-step synthesis of cationic block copolymers of poly(2-N-(dimethylaminoethyl) methacrylate) (pDMAEMA) and copolymers of poly(propylene oxide) (PPO) and poly(ethylene oxide) (PEO) has been developed. The PEO-PPO-PEO-pDMAEMA (L92-pDMAEMA) and PEO-pDMAEMA copolymers were obtained via free radical polymerization of DALA-EMA initiated by polyether radicals generated by cerium(IV). Over 95% of the copolymer fraction was of molecular mass ranging from 6.9 to 7.1 kDa in size, indicating the prevalence of the polyether-monoradical initiation mechanism. The L92-pDMAEMA copolymers possess parent surfactant-like surface activity. In contrast, the PEO-pDMAEMA copolymers lack significant surface activity. Both copolymers can complex with DNA. Hydrodynamic radii of the complexes of the L92-pDMAEMA and PEO-pDMAEMA with plasmid DNA ranged in size from 60 to 400 nm, depending on the copolymer/DNA ratio. Addition of Pluronic P123 to the L92-pDMAEMA complexes with DNA masked charges and decreased the tendency of the complex to aggregate, even at stoichiometric polycation/DNA ratios. The transfection efficiency of the L92-pDMAEMA copolymer was by far greater than that of the PEO-pDMAEMA copolymer. An extra added Pluronic P123 further increased the transfecton efficacy of L92-pDMAEMA, but did not affect that of PEO-pDMAEMA.
引用
收藏
页码:626 / 633
页数:8
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