State Key Laboratory of Chemical Resource Engineering, Key Laboratory of Carbon Fiber and Functional Polymers, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, People's Republic of China.
Acta Biomater. 2011 Aug;7(8):3131-40. doi: 10.1016/j.actbio.2011.04.023. Epub 2011 May 3.
Cationic polymers with low cytotoxicity and high transfection efficiency have attracted considerable attention as non-viral carriers for gene delivery. Recently we reported that ethanolamine (EA)-functionalized poly(glycidyl methacrylate) (PGMA) (termed PGEA) vectors can have excellent transfection efficiency, while exhibiting very low toxicity. Herein different EA- and ethylenediamine (ED)-functionalized PGMA (termed PGEAED) vectors, as well as ED-functionalized PGMA (termed PGED) vectors, are proposed and compared for efficient gene delivery. In addition to the cationic pendant secondary amine and hydroxyl groups of PGEA, PGEAED, and PGED also contain flanking primary amine groups. PGEAED and PGED exhibited a substantially enhanced ability to condense pDNA into complex nanoparticles at the 100 nm level with positive zeta potentials of about 30 mV at nitrogen/phosphate (N/P) ratios of 10 or higher. More interestingly, no obvious change in the cytotoxicity of PGEAED was observed with a substantial increase in ED content. Moreover, the flanking primary amine groups induced by ED could be readily functionalized by glycyrrhetinic acid or cholic acid to improve the biophysical properties of the gene vectors.
带正电荷的聚合物细胞毒性低、转染效率高，作为非病毒载体在基因传递方面受到广泛关注。最近我们报道了乙醇胺（EA）功能化聚（甲基丙烯酸缩水甘油酯）（PGMA）（称为 PGEA）载体具有极好的转染效率，同时表现出非常低的毒性。在此，我们提出并比较了不同的 EA 和乙二胺（ED）功能化 PGMA（称为 PGEAED）载体以及 ED 功能化 PGMA（称为 PGED）载体，以实现高效的基因传递。除了 PGEA 的阳离子侧链仲胺和羟基外，PGEAED 和 PGED 还含有侧翼伯胺基团。PGEAED 和 PGED 能够在氮/磷（N/P）比为 10 或更高时将 pDNA 凝聚成正 zeta 电位约为 30 mV 的 100nm 级复合纳米颗粒，能力显著增强。更有趣的是，随着 ED 含量的增加，PGEAED 的细胞毒性没有明显变化。此外，ED 诱导的侧翼伯胺基团可以很容易地被甘草次酸或胆酸功能化，从而改善基因载体的生物物理性质。
