表面与内核的组成结构对pdmaema基两亲性共聚物纳米粒基因递送功效的影响-材料化学工程专业论文.docxVIP

potential, gel electrophoresis, endocytosis and transfection both in vitro and in vivo, and evaluated function of polyanions with different PEG grafting rate on gene delivery. As the outer layer of the ternary complex components, HP, compared to GP, presented better positive charge shield ability on surface of binary complex NP-D, effectively improve cell compatibility. Through HA performance of tumor cell-specific receptor-mediated endocytosis and hyaluronidase (Hyal-1) degradation of the response characteristics to deshelling both intracellular and extracellular, tumor cells endocytosis and endosomes escape ability were efficiently improved, as a result increasing cell transfection efficiency in vitro and tumor targeted delivery in vivo. To further explore the structure contribution of the hydrophobic segments to DNA binding, endocytosis and gene transfection efficiency, we synthesized different block cationic copolymer PEG-PCL-PDMAEMA (PEC) with different molecular weights of PCL and cyclic ether side groups modified PCL block copolymers to explore effects of hydrophobic segment structure. The results presented that the increase of PCL molecular weight can enhance the resistance of PEC NPs/DNA to enzymatic degradation of DNA, promote cell binding and improve endocytosis and transfection efficiency. The introduction of cyclic ether side groups in PCL segment can improve transfection efficiency, yet its functional mechanism need to be further explored. Keywords: Polyglutamic acid; Hyaluronic acid; Hydrophobic modification; Amphiphilic cationic copolymers; Ternary complex; Gene delivery 目 录 第一章 前 言 1 第二章 文献综述 2 2.1 肿瘤细胞生长以及递送障碍 2 2.2 聚乙二醇化的研究进展 4 2.3 双亲性聚合物的研究进展 5 2.4 三元复合物研究进展 10 2.5 研究目的和内容 12 第三章 PCL-g-PDMAEMA NPs/DNA/PGA-g-PEG 三元复合物基因递送系统的研究 13 3.1 引言 13 3.2 实验部分 14 3.2.1 实验原料 14 FITC 标记的 PCL-g-PDMAEMA 以及聚乙二醇化 PGA 的合成 14 聚合物 1H NMR 表征 15 3.2.4 质粒提取 15 3.2.5 聚合物纳米粒子以及复合物的制备 15 3.2.6 三元复合物表征 16 3.2.7 细胞培养 16 3.2.8 体外转染实验 16 3.2.9 复合物对细胞的摄取 17 3.