基于间苯二甲醛构建的IPEI在滑膜细胞中的转染与毒性研究

Transfection and Cytotoxicity Studies of Novel PEI Derivative IPEI in Synovial Cells

目的:研究以间苯二甲醛(Isophthalaldehyde)作为连接剂构建的新型聚乙烯亚胺(Polyethyleneimine,PEI)衍生物IPEI为非病毒基因载体在治疗类风湿性关节炎(RA)中的应用,主要对阳离子聚合物IPEI在SD大鼠滑膜细胞中进行体外生物学评价。方法:IPEI以不同质量比包裹绿色荧光蛋白(GFP)质粒和白细胞介素-1受体拮抗剂(IL-1Ra)质粒,研究复合物在滑膜细胞中的转染活性,同时用MTT方法研究聚合物对滑膜细胞的细胞毒性。结果:复合物在质量比为2到10范围内,转染效果比较理想,具有高效输送质粒的能力;同时IPEI的细胞毒性也很小,细胞存活率明显高于商业化转染试剂PEI 25 KDa对照组。结论:阳离子聚合物IPEI具有高转染效率和低毒性的特点,从体内水平上证实了IPEI是一种良好的治疗类风湿性关节炎的基因输送载体。

Objective： Novel PEI derivative IPEI is designed and synthesized by using isophthalaldehyde as linkers. This study is to investigate the transfection efficiency and cell cytotoxicity of IPEI, which can be applied as non-viral carriers in rheumatoid arthritis gene therapy. Methods： IPEI was packed with GFP and IL-1Ra pDNA at different mass ratios, transfection efficiency of this polyplex in synovial cells of SD rats was investigated. Cytotoxicity of 1PEI was detected by MTT method. Results： IPEI could effectively deliver pDNA into synovial cells to express related protein, especially when mass ratio was 2 to 10;IPEI had lower cytotoxicity than commercial transfection agent PE125 KDa at the same concentration and the cell viability was very high. Conclusions： 1PEI had high transfection efficiency and low cytotoxicity, indicating that it had a bright application prospect in rheumatoid arthritis gene therapy as non-viral carriers.