Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
J Control Release. 2011 May 30;152(1):135-42. doi: 10.1016/j.jconrel.2011.03.025. Epub 2011 Mar 30.
Cationic polymers play an important role in gene delivery. To search for potential non-viral gene carriers, a series of biodegradable cationic polymers, poly(ethylene glycol)-block-poly(carbonates-graft-oligoethylenimine) [mPEG-b-P(MCC-g-OEI), PPO] copolymers, were synthesized by grafting different kinds of oligoethylenimine (OEI) to the same biodegradable backbone, a derivative of poly(ethylene glycol)-block-polycarbonates. The as-synthesized PPO copolymers were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, and gel permeation chromatography. Two of the as-synthesized PPO copolymers (PPO600 and PPO1800) could efficiently condense DNA into nanosized particles (100-140 nm) with positive surface charges when the PPO/DNA mass ratio is above 10:1. The cell toxicity and gene transfection evaluations show that PPO copolymers, especially PPO1800, which exhibits lower cytotoxicity and higher gene transfection efficiency than PEI25K in the absence and the presence of serum in the CHO and COS-7 cell lines, have great potential as non-viral gene carriers. The PPO1800 copolymer images obtained by confocal laser scanning microscopy prove that PPO copolymers could efficiently mediate the entry of plasmid DNA into cells. These results show that PPO copolymers may be potential non-viral gene carriers in future applications of gene therapy.
阳离子聚合物在基因传递中起着重要作用。为了寻找潜在的非病毒基因载体，我们合成了一系列可生物降解的阳离子聚合物，聚乙二醇-嵌段-聚（碳酸酯-接枝-低聚亚乙基亚胺）[mPEG-b-P（MCC-g-OEI），PPO]共聚物，通过将不同种类的低聚亚乙基亚胺（OEI）接枝到相同的可生物降解的聚乙二醇-聚碳酸酯衍生物的骨架上。所合成的 PPO 共聚物通过傅里叶变换红外光谱、核磁共振光谱和凝胶渗透色谱进行了表征。所合成的两种 PPO 共聚物（PPO600 和 PPO1800）在 PPO/DNA 质量比高于 10:1 时，可以有效地将 DNA 凝聚成带正电荷的纳米颗粒（100-140nm）。细胞毒性和基因转染评价表明，PPO 共聚物，特别是 PPO1800，在 CHO 和 COS-7 细胞系中，无论是在无血清还是有血清的情况下，其细胞毒性都比 PEI25K 低，基因转染效率都比 PEI25K 高，具有作为非病毒基因载体的巨大潜力。通过共聚焦激光扫描显微镜获得的 PPO1800 共聚物图像证明 PPO 共聚物可以有效地介导质粒 DNA 进入细胞。这些结果表明 PPO 共聚物可能是未来基因治疗应用中的潜在非病毒基因载体。
