本文選題：基因載體 + 氧化硅納米顆粒��； 參考：《北京化工大學(xué)》2015年碩士論文

【摘要】：氧化硅納米顆粒形貌可控、易于表面功能化、具有良好的生物相容性和生物可降解性,是一種極有潛力的安全高效非病毒性基因載體材料。以低分子量陽(yáng)離子聚合物修飾氧化硅表面將有效提高載體的轉(zhuǎn)染效率并降低細(xì)胞毒性。此外,氧化硅納米顆粒的形貌和尺寸影響其與細(xì)胞和生物系統(tǒng)的相互作用,這意味著特殊形貌的氧化硅基因載體可能具有更好的轉(zhuǎn)染效果。本文制備了一系列形貌、尺寸不同的氧化硅納米顆粒,將陽(yáng)離子聚合物引入其表面,探究了載體形貌和尺寸對(duì)基因轉(zhuǎn)染效率的影響。隨后,我們以不同尺寸特殊形貌的(星形)氧化硅空心納米顆粒為基質(zhì),制備了一種具有還原響應(yīng)性的基因/藥物雙功能載體,使基因治療和藥物治療發(fā)揮協(xié)同抗癌效應(yīng)。主要工作如下：1、以不同形貌的氧化硅納米顆粒為基質(zhì),利用ATRP法對(duì)其表面進(jìn)行PDMAEMA功能化,得到陽(yáng)離子聚合物功能化的氧化硅(SiO2-g-PDMAEMA)基因載體,以探究納米顆粒形貌和尺寸對(duì)基因轉(zhuǎn)染效率的影響。對(duì)SiO2-g-PDMAEMA的DNA絡(luò)合能力、細(xì)胞毒性和轉(zhuǎn)染效率進(jìn)行了詳細(xì)研究。實(shí)驗(yàn)結(jié)果表明,軸徑比大的手性納米棒轉(zhuǎn)染效率最高且毒性適中。此外,空心氧化硅納米球比實(shí)心結(jié)構(gòu)表現(xiàn)出了更好的轉(zhuǎn)染能力。本實(shí)驗(yàn)為制備基因載體提供了新的思路。2、以六角星形空心氧化硅納米顆粒(SHNPs)為基質(zhì),得到了種具有智能響應(yīng)性分子開(kāi)關(guān)的藥物／基因共載體(SHNP-PGEA)。SHNPs表面通過(guò)雙硫鍵接入Ad,利用Ad與β-CD的超分子自組裝作用引入CD-PGEA。所制得的SHNP-PGEA具有智能分子開(kāi)關(guān),可實(shí)現(xiàn)零過(guò)早藥物釋放,并在癌細(xì)胞高濃度GSH作用下釋放藥物。SHNP-PGEA還具有良好的運(yùn)載DNA的能力。對(duì)SHNP-PGEA的DNA絡(luò)合能力、基因轉(zhuǎn)染效率、藥物釋放行為和協(xié)同抗癌效應(yīng)進(jìn)行了詳細(xì)研究。實(shí)驗(yàn)結(jié)果表明,與傳統(tǒng)氧化硅空心球(HNP)相比,六角星形的SHNP-PGEA表現(xiàn)出了更高的轉(zhuǎn)染效率、更好的細(xì)胞內(nèi)吞效果和抗癌效果。以SHNPs為基質(zhì)的多功能載體在癌癥治療領(lǐng)域具有廣泛的應(yīng)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.
【學(xué)位授予單位】：北京化工大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類(lèi)號(hào)】：O613.72;TB383.1

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本文編號(hào)：1861640