非球形含糖纳米粒子的合成及与蛋白和细胞作用研究

发布时间：2018-11-18 07:30

【摘要】：人工合成的侧链含有糖组分的含糖聚合物(glycopolymer)能够与凝集素以多价交互的方式进行作用,这种方法与天然糖蛋白的作用类似。纳米粒子(NPs)具有极大的表面/体积比和有限的尺寸,使得其与大体积材料相比,具有独特的光学、力学、热力学等性质,纳米粒子在纳米医学以及其他生物医学方面具有巨大的潜在应用前景。表面修饰上含糖聚合物的纳米粒子是一类重要的生物活性粒子,具有重要的研究价值。目前,人工合成的含糖纳米粒子(glyco-nanoparticles)多为球形,理论和实验研究都发现,形状对含糖纳米粒子生物性能和应用具有显著影响。为了探究这种影响效果,我们合成了两种不同形状非球形的含糖纳米粒子,并通过生物实验研究它们与蛋白、细胞的识别能力。本论文主要研究如下:(1)非球形聚糖修饰的氧化铁纳米粒子(Glyco-IONPs)的合成本研究首次将无机纳米粒子合成以及仿生化学和“硫醇-烯”点击化学结合,制备了两种均一性较好,不同形状的含糖氧化铁纳米粒子。首先,我们制备了两种不同形状的氧化铁纳米粒子(纺锤状、立方体),然后以它们为核,通过“catecholic chemistry”在其表面包裹上含有双键的多巴胺甲基丙烯酰胺(DMA)。采用可逆加成-断裂链转移(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”点击化学将PMAG修饰到DMA包裹的氧化铁纳米粒子表面。实验结果表明,合成的含糖纳米粒子形状可控,表面聚糖的质量分数固定。(2)非球形含糖纳米粒子的生物活性本研究通过分析比较两种不同形状含糖氧化铁纳米粒子与蛋白和细胞作用效果,探究了形状对细胞吞入纳米粒子数目的影响。首先,通过与不同类型凝集素的作用,研究Glyco-IONPs对特异性蛋白(Con A)的识别功能。然后通过细胞实验探究形状对含糖纳米粒子与细胞作用的影响。实验结果表明,合成的纺锤状、立方体含糖纳米粒子水溶性良好,在血清中可以稳定存在,与特异性蛋白具有很好的吸附性。并且,细胞与含糖纳米粒子的作用效果受粒子形状的影响,细胞对立方体形含糖纳米粒子的吞入效果要高于纺锤状纳米粒子。
[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.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：TB383.1

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