【摘要】：人工合成的側(cè)鏈含有糖組分的含糖聚合物(glycopolymer)能夠與凝集素以多價交互的方式進行作用,這種方法與天然糖蛋白的作用類似。納米粒子(NPs)具有極大的表面/體積比和有限的尺寸,使得其與大體積材料相比,具有獨特的光學(xué)、力學(xué)、熱力學(xué)等性質(zhì),納米粒子在納米醫(yī)學(xué)以及其他生物醫(yī)學(xué)方面具有巨大的潛在應(yīng)用前景。表面修飾上含糖聚合物的納米粒子是一類重要的生物活性粒子,具有重要的研究價值。目前,人工合成的含糖納米粒子(glyco-nanoparticles)多為球形,理論和實驗研究都發(fā)現(xiàn),形狀對含糖納米粒子生物性能和應(yīng)用具有顯著影響。為了探究這種影響效果,我們合成了兩種不同形狀非球形的含糖納米粒子,并通過生物實驗研究它們與蛋白、細(xì)胞的識別能力。本論文主要研究如下:(1)非球形聚糖修飾的氧化鐵納米粒子(Glyco-IONPs)的合成本研究首次將無機納米粒子合成以及仿生化學(xué)和“硫醇-烯”點擊化學(xué)結(jié)合,制備了兩種均一性較好,不同形狀的含糖氧化鐵納米粒子。首先,我們制備了兩種不同形狀的氧化鐵納米粒子(紡錘狀、立方體),然后以它們?yōu)楹?通過“catecholic chemistry”在其表面包裹上含有雙鍵的多巴胺甲基丙烯酰胺(DMA)。采用可逆加成-斷裂鏈轉(zhuǎn)移(RAFT)聚合方法合成了一系列分子量可控的含糖聚合物(PMAG),最后利用“硫醇-烯”點擊化學(xué)將PMAG修飾到DMA包裹的氧化鐵納米粒子表面。實驗結(jié)果表明,合成的含糖納米粒子形狀可控,表面聚糖的質(zhì)量分?jǐn)?shù)固定。(2)非球形含糖納米粒子的生物活性本研究通過分析比較兩種不同形狀含糖氧化鐵納米粒子與蛋白和細(xì)胞作用效果,探究了形狀對細(xì)胞吞入納米粒子數(shù)目的影響。首先,通過與不同類型凝集素的作用,研究Glyco-IONPs對特異性蛋白(Con A)的識別功能。然后通過細(xì)胞實驗探究形狀對含糖納米粒子與細(xì)胞作用的影響。實驗結(jié)果表明,合成的紡錘狀、立方體含糖納米粒子水溶性良好,在血清中可以穩(wěn)定存在,與特異性蛋白具有很好的吸附性。并且,細(xì)胞與含糖納米粒子的作用效果受粒子形狀的影響,細(xì)胞對立方體形含糖納米粒子的吞入效果要高于紡錘狀納米粒子。
[Abstract]:Synthetic side chain sugar containing polymer (glycopolymer) can interact with agglutinin in a multivalent manner, which is similar to that of natural glycoprotein. Nano-particle (NPs) has a great surface / volume ratio and a limited size, which makes it have unique optical, mechanical, thermodynamic and other properties compared with large volume materials. Nanoparticles have great potential applications in nanomedicine and other biomedical applications. As an important class of bioactive particles, sucrose polymer nanoparticles on surface modification have important research value. At present, the synthetic sucrose nanoparticles (glyco-nanoparticles) are mostly spherical. Both theoretical and experimental studies show that the shape has a significant impact on the biological properties and applications of sucrose nanoparticles. In order to investigate the effect, we synthesized two kinds of non-spherical sugar nanoparticles with different shapes, and studied their ability to recognize proteins and cells through biological experiments. The main results of this thesis are as follows: (1) Synthesis of Glyco-IONPs nanoparticles modified by non-globular glycan. In this study, inorganic nanoparticles were synthesized and bionic chemistry and mercaptan click-chemistry were combined for the first time. Two kinds of sugary ferric oxide nanoparticles with good homogeneity and different shapes were prepared. First, we prepared two different shapes of iron oxide nanoparticles (spindles, cubes), and then, using them as the core, we encapsulated the dopamine methacrylamide (DMA). On its surface by "catecholic chemistry". A series of sugary polymer (PMAG), with controllable molecular weight were synthesized by reversible addition-break chain transfer (RAFT) polymerization. Finally, PMAG was modified onto the surface of DMA coated iron oxide nanoparticles by "mercaptan-enene" click-chemistry. The experimental results show that the shape of the synthesized sugar nanoparticles is controllable. (2) Biological activity of non-spherical sucrose nanoparticles. The effects of two different shapes of carbohydrate iron oxide nanoparticles on protein and cell interaction were analyzed and compared. The effect of shape on the number of nanoparticles swallowed by cells was investigated. Firstly, the recognition function of Glyco-IONPs on specific protein (Con A) was studied by interaction with different types of lectins. Then the effects of shape on the interaction of sugar-containing nanoparticles with cells were investigated by cell experiments. The experimental results show that the synthesized spindle-like cubic sucrose nanoparticles are water-soluble and can exist stably in serum and have good adsorption with specific proteins. Moreover, the effect of cell interaction with sugar nanoparticles is affected by the shape of particles, and the effect of cells on the ingestion of cubic sugar nanoparticles is higher than that of spindle-shaped nanoparticles.
【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：TB383.1

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