特殊形貌氧化硅纳米颗粒在基因载体中的应用

发布时间：2018-05-08 13:44

本文选题：基因载体 + 氧化硅纳米颗粒　；参考：《北京化工大学》2015年硕士论文

【摘要】：氧化硅纳米颗粒形貌可控、易于表面功能化、具有良好的生物相容性和生物可降解性,是一种极有潜力的安全高效非病毒性基因载体材料。以低分子量阳离子聚合物修饰氧化硅表面将有效提高载体的转染效率并降低细胞毒性。此外,氧化硅纳米颗粒的形貌和尺寸影响其与细胞和生物系统的相互作用,这意味着特殊形貌的氧化硅基因载体可能具有更好的转染效果。本文制备了一系列形貌、尺寸不同的氧化硅纳米颗粒,将阳离子聚合物引入其表面,探究了载体形貌和尺寸对基因转染效率的影响。随后,我们以不同尺寸特殊形貌的(星形)氧化硅空心纳米颗粒为基质,制备了一种具有还原响应性的基因/药物双功能载体,使基因治疗和药物治疗发挥协同抗癌效应。主要工作如下：1、以不同形貌的氧化硅纳米颗粒为基质,利用ATRP法对其表面进行PDMAEMA功能化,得到阳离子聚合物功能化的氧化硅(SiO2-g-PDMAEMA)基因载体,以探究纳米颗粒形貌和尺寸对基因转染效率的影响。对SiO2-g-PDMAEMA的DNA络合能力、细胞毒性和转染效率进行了详细研究。实验结果表明,轴径比大的手性纳米棒转染效率最高且毒性适中。此外,空心氧化硅纳米球比实心结构表现出了更好的转染能力。本实验为制备基因载体提供了新的思路。2、以六角星形空心氧化硅纳米颗粒(SHNPs)为基质,得到了种具有智能响应性分子开关的药物／基因共载体(SHNP-PGEA)。SHNPs表面通过双硫键接入Ad,利用Ad与β-CD的超分子自组装作用引入CD-PGEA。所制得的SHNP-PGEA具有智能分子开关,可实现零过早药物释放,并在癌细胞高浓度GSH作用下释放药物。SHNP-PGEA还具有良好的运载DNA的能力。对SHNP-PGEA的DNA络合能力、基因转染效率、药物释放行为和协同抗癌效应进行了详细研究。实验结果表明,与传统氧化硅空心球(HNP)相比,六角星形的SHNP-PGEA表现出了更高的转染效率、更好的细胞内吞效果和抗癌效果。以SHNPs为基质的多功能载体在癌症治疗领域具有广泛的应用前景。
[Abstract]:Because of its controllable morphology, easy surface functionalization and good biocompatibility and biodegradability, silicon oxide nanoparticles are potential non-viral gene carriers. Modification of silicon oxide surface with low molecular weight cationic polymer can effectively improve the transfection efficiency and decrease the cytotoxicity of the vector. In addition, the morphology and size of silicon oxide nanoparticles affect their interaction with cells and biological systems, which means that the special morphology of silicon oxide gene vector may have better transfection effect. In this paper, a series of silicon oxide nanoparticles with different size and morphology were prepared. Cationic polymers were introduced into the surface to investigate the effects of the morphology and size of the carrier on the efficiency of gene transfection. Subsequently, we prepared a novel gene / drug bifunctional vector with different size and special morphology of (star) silica hollow nanoparticles as the matrix, which can make gene therapy and drug therapy play a synergistic anticancer effect. The main work is as follows: 1. The surface of silica nanoparticles with different morphologies was functionalized by PDMAEMA by ATRP method, and the cationic polymer functionalized SiO2-g-PDMAEMAA gene vector was obtained. To explore the effect of the morphology and size of nanoparticles on gene transfection efficiency. The DNA complexation ability, cytotoxicity and transfection efficiency of SiO2-g-PDMAEMA were studied in detail. The experimental results show that the chiral nanorods with high axial diameter ratio have the highest transfection efficiency and moderate toxicity. In addition, hollow silica nanospheres showed better transfection ability than solid structures. This study provides a new way of thinking for the preparation of gene vectors, which is based on the hexagonal star hollow silica nanoparticles (SHNPs). A novel drug / gene covector, SHNP-PGEAA 路SHNPs, which has intelligent response molecular switch, was obtained. The surface of SHNP-PGEAA 路SHNPs was connected with Advia via disulfide bond, and CD-PGEA-1 was introduced by using the supramolecular self-assembly interaction between Ad and 尾 -CD. The prepared SHNP-PGEA has an intelligent molecular switch, which can realize zero premature drug release, and can release the drug .SHNP-PGEA under the action of high concentration of GSH in cancer cells. SHNP-PGEA also has a good ability to transport DNA. The DNA complexation ability, gene transfection efficiency, drug release behavior and synergistic anticancer effect of SHNP-PGEA were studied in detail. The experimental results showed that the hexagonal star SHNP-PGEA showed higher transfection efficiency, better endocytosis and anticancer effect than traditional silica hollow sphere. The multifunctional vector based on SHNPs has a wide application prospect in the field of cancer treatment.
【学位授予单位】：北京化工大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：O613.72;TB383.1

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