针对阳离子性载体材料在完成DNA转运和释放后形成对细胞正常生长过程的干扰,设计了一利情&够在细胞中水解回复到电中性的叔胺型聚羧酸甜菜碱酯(pCB-ester),研究了该聚合物对细胞生长行为的影响,以及初步的基因转染效果。结果表明pCB-ester的细胞毒性远小于经典的体外高效转染材料聚乙烯亚胺(PEI,25KDa)和其结构类似物聚甲基丙烯酸二甲氨乙酯(pDMAEMA),并在pCB-ester/DNA的N/P大于1/1时能有效包载DNA,显示了初步的DNA转染能力。这种pCB-ester低细胞毒性特性可能与其在细胞中水解形成两性离子,降低与细胞内生物大分子的非特异性相互作用有关。通过优化聚合物结构,有望进一步提高pCB-ester的转染效率,使之成为新一代超低毒性的非病毒基因载体。
To overcome the interference of the polycationic polymer on the normal cell growth after DNA released, a poly (carboxybetaine methacrylate ester) with tertiary amine (pCB-ester) was designed, which could hydrolyze back to the neutral state inside the cell. The results show that the cytotoxicity of pCB-ester is much lower than either the polyethyleneimine (PEI, 25 KDa) which is the classic material with high in vitro transfeetion efficiency or the poly dimethylamino ethyl methacrylate (pDMAEMA) which has a structural analogous to pCB-ester. At the same time the pCB-ester could successfully wrap up the DNA when the N/P ratio is over 1/1, and this DNA/polymer complex shows a low transgene expression with primary level. It was believed that the low cytotoxicity of pCB-ester benefits from its hydrolyzed zwitterionic structure, which reduces the non-specific interaction between pCB with biomacromolecules inside the cell. It was expected that a new non-viral gene vector with ultra-low cytotoxicity and high transgene expression level could be realized through optimizing.the structure of the prepared pCB-ester.