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目的制备阳离子超支化缩水甘油醚衍生物HPG-AGE-cys(HPAC),将其包裹在腺病毒(r Ad)表面形成复合物,探究其提高腺病毒基因表达效率的能力。方法采用阴离子开环聚合反应制备超支化缩水甘油醚,并进一步阳离子衍生化得到HPAC,其结构经核磁确证;通过静电复合作用制备材料-腺病毒复合物,并测定其粒径和Zeta电位,用透射电镜观察其表面形态;考察了复合物被A549细胞、CHO细胞和MDCK细胞摄取的能力和细胞转导的能力。结果成功合成了阳离子超支化缩水甘油醚衍生物HPAC,制备了HPAC-r Ad复合物。其平均粒径为128.8±3.8 nm,Zeta电位为29.8±5.2 m V;与裸病毒r Ad比较,复合物被细胞摄取的能力和细胞转导的能力均有显著提高。结论阳离子超支化缩水甘油醚衍生物材料合成方法简单易行,制备的HPAC-r Ad复合物能够显著提高病毒的基因效率,在腺病毒的基因传递方面具有广阔的应用前景。
OBJECTIVE: To prepare HPG-AGE-cys (HPAC), a cationic hyperbranched glycidyl ether derivative, and enclose it in the surface of adenovirus (r Ad) to form a complex and explore its ability to improve the efficiency of adenovirus gene expression. Methods Anionic ring-opening polymerization was used to prepare hyperbranched glycidyl ethers. Further cationic derivatization was used to obtain HPAC. The structure was confirmed by nuclear magnetic resonance (NMR). The material-adenovirus complex was prepared by electrostatic complexation and its particle size and zeta potential were measured. The surface morphology of the complex was observed by transmission electron microscopy. The ability of the complex to uptake by A549 cells, CHO cells and MDCK cells and the ability of cell transduction were investigated. Results The cationic hyperbranched glycidyl ether derivative HPAC was successfully synthesized and the HPAC-r Ad complex was prepared. The average particle size was 128.8 ± 3.8 nm and the Zeta potential was 29.8 ± 5.2 mV. Compared with the nude virus Ad, the complex was significantly up-regulated by cellular uptake and cell transduction capacity. Conclusion The synthesis of cationic hyperbranched glycidyl ether derivatives is simple and easy. The prepared HPAC-r Ad complex can significantly improve the gene efficiency of the virus and has broad application prospects in the gene delivery of adenovirus.