中文摘要：

通过分散聚合的方法,以改性了双键的葡聚糖（Dex-AA）作为交联剂,甲基丙烯酸二甲氨基乙酯（DMAEMA）作为单体,过硫酸铵（APS）和四甲基乙二胺（TEMED）分别作为引发剂和助引发剂,合成了不同交联度的、具有pH敏感内吞增强作用的葡聚糖纳米凝胶（DD-NGs）,并测试了其复合siRNA进行转染的能力.实验结果表明,该纳米凝胶表面带有正电荷,具有较好的担载siRNA进入肿瘤细胞并沉默基因的能力,且具有pH响应粒径变化的性质.在pH=7.4的体液环境中,纳米凝胶与基因的复合物粒子较小;在肿瘤酸性（pH=6.8）条件下,纳米凝胶与基因的复合物粒子变大,显著地增强了肿瘤细胞对纳米凝胶与基因复合物的内吞.

英文摘要：

pH responsivenanogels（DD-NGs） with different degrees of crosslinking were synthesized through dispersion polymerization. In this polymerization, dextran modified with acrylic acid（Dex-AA） served as the crosslinker. 2-（Dimethylamino） ethyl methacrylate（DMAEMA） was the monomer, thus the nanogels changed the particle size at different pH values. Ammonium persulfate（APS） and tetramethylethylenediamine（TEMED） were the initiator and the promoter, respectively. The structure and ability of mediating siRNA transfection of the DD-NGs were characterized. Also, for the DD-NGs/siRNA complexes, their particle size, zeta potential, TEM assay, pH sensitive cellular uptake（by confocal laser scan microscopy and flow cytometry） were investigated. The results indicated that the DD-NGs/siRNA complexes were positively charged and DD-NGs could mediate siRNA into tumor cells. Both in He La-Luc cells and Huh7-Luc cells, the complexes of the two kinds of DD-NGs and siRNA downregulated about 50% luciferase reporter gene, indicating an excellent efficiency of gene silencing. Moreover, the cellular cytotoxicity assay was performed, and both DD-NGs showed non-cytotoxicity compared with PEI25 k toward He La-Luc cells and Huh7-Luc cells, achieving 70% cell viability at the concentration of 0.1 mg/m L. The DD-NGs/siRNA complexes showed positive charge（13-15 m V）, and suitable particle size（50-100 nm） for systemic circulation at physiological pH（pH = 7.4）, but the complexes swelled to a much larger particle size（150-250 nm） at tumor matrix（pH = 6.8）, revealing a particle size changeable property with pH. Particle size measurement and TEM assay accurately supported this conclusion. Finally, flow cytometry assay was conducted to measure quantitatively the cellular uptake ability of the DD-NGs/siRNA complexes by He La-Luc cells at pH = 7.4 and 6.8. Because of the variation in particle size, an enhanced cellular uptake at tumor matrix（pH = 6.8） was obtained compared with the physiological condition