基于聚乙烯亚胺衍生物的功能化复合物的合成及其作为基因载体的性能研究

发布时间：2018-03-13 08:16

本文选题：聚乙烯亚胺　切入点：基因载体　出处：《天津理工大学》2017年硕士论文　论文类型：学位论文

【摘要】：在非病毒基因载体中,聚乙烯亚胺(PEI)阳离子基因载体转染效率极高,但却有很高的细胞毒性,需要进行优化。在此,我们构建了两种基于PEI的基因载体。在体系一中,我们用环糊精(CD)交联低分子量的PEI制得PEI-CD,用聚乙二醇修饰偶氮苯(Az)得到PEG-Az,以主客体作用构建光刺激响应性的PEI-CD/PEG-Az/DNA复合体。电势测量发现,聚乙二醇的引入能有效降低复合物纳米粒子的电势,但在光刺激下并不能使PEG完全脱落,故选用谷胱甘肽响应的二硫键连接Az与PEG,构建PEI-CD/PEG-SS-Az/DNA复合体,它在光照与谷胱甘肽(GSH)的双重作用下使PEG完全脱落,促进DNA释放。在体系二中,我们用苯硼酸修饰的PEI(PEI_(25000)-PBA)以及四羧基四苯基乙烯(TPE-(COOH)4)交联聚合的PEI(PEI_(1800)-TPE)与DNA混合,制得PEI_(1800)-TPE/PEI_(25000)-PBA/DNA复合物纳米粒子,该纳米粒子中PBA的存在使其具有膜靶向性,可促进基因载体进入细胞。同时,TPE衍生物的聚集诱导发光效应能有效追踪该基因载体在细胞内的运转过程,使基因载体在细胞内的运转机制变得可视化。
[Abstract]:In the non-viral gene vector, polyvinyleneimine (PEI) cationic gene vector is highly efficient, but it has high cytotoxicity and needs to be optimized. In this paper, we constructed two kinds of gene vectors based on PEI. PEI-CD was prepared by crosslinking low molecular weight PEI with cyclodextrin, and PEG-Az-modified by polyethylene glycol (PEG-Azazo). The photostimulation-responsive PEI-CD/PEG-Az/DNA complex was constructed by host-guest interaction. The introduction of polyethylene glycol can effectively reduce the electric potential of composite nanoparticles, but it can not completely shed PEG under photostimulation. Therefore, glutathione-responsive disulfide bond is used to connect Az and PEG to construct PEI-CD/PEG-SS-Az/DNA complex. In system 2, PEIPEI-1 modified with benzoboric acid was used to modify PEII-PEII-PBA) and tetracarboxylic tetraphenylethylene tetrachloroethylene (TPE-COOHH4) was crosslinked and polymerized, PEIPEII-PEII-PEI-1) was mixed with DNA. The PEI_(1800)-TPE/PEI_(25000)-PBA/DNA complex nanoparticles were prepared. The presence of PBA in the nanoparticles made them membrane targeting and promoted the entry of gene vectors into cells. At the same time, the aggregation induced luminescence effect of PEI_(1800)-TPE/PEI_(25000)-PBA/DNA derivatives can effectively track the translocation of the gene vectors in cells. To visualize the mechanism of gene vector translocation in cells.
【学位授予单位】：天津理工大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：Q78

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