氧化石墨烯基非共价修饰纳米复合材料的制备及其在药物递送方面的应用

发布时间：2018-06-18 02:33

本文选题：氧化石墨烯 + 层层自组装　；参考：《江苏大学》2017年硕士论文

【摘要】：癌症一直是严重危害人类健康的一个话题,为了提高抗癌效率以及减轻治疗过程中对机体的毒副作用,人们对此设计了许多药物运输系统。其中,纳米材料介导的药物运输系统吸引了广泛的关注。在众多纳米材料当中,氧化石墨烯(GO)由于其具有水溶性,有较大的适于药物负载的比表面积等优异特性而被广泛应用于载药领域。尽管氧化石墨烯有许多优异特性,但其在生理条件下易聚集,因此,增强其在生理条件下的溶解性成为了解决问题的关键。其中,对GO进行表面的修饰可以增强它在生理条件下的溶解性。层层自组装技术是纳米粒表面修饰的一个很重要的技术,它主要是通过在纳米粒子表面逐步沉积带相反电荷的聚电解质来形成壳核纳米结构。然而,在氧化石墨烯纳米片层表面层层堆积带电荷的聚合电解质并将其作为抗癌药物运输载体的研究仍然处在初始阶段。在本论文中,我们分别用了两个带相反电荷的多聚电解质,壳聚糖(CS)和海藻酸钠(SA),壳聚糖(CS)和葡聚糖(Dex),鱼精蛋白(PRM)和海藻酸钠(SA)作为膜材,利用层层自组装技术,分别合成了GO-CS-SA,GO-CS-Dex和GO-PRM-SA纳米复合物。然后用FTIR、zeta电位和AFM等方法对其进行表征,其次进一步对复合物的稳定性,非特异性蛋白吸附进行研究。最后,对该纳米复合物进行抗癌药物阿霉素(DOX)的负载,对其药物负载,药物释放,以及细胞毒性行为进行考察。具体研究结果如下:1.以GO为基体,带有反向电荷的CS和SA、CS和Dex为聚电解质,通过层层自组装技术分别合成了GO-CS-SA,GO-CS-Dex复合物。采用FTIR、AFM、Zeta电位、TGA等方法对其进行表征,结果表明CS和SA,CS和Dex成功覆在了GO表面。稳定性试验及非特异性蛋白吸附试验表明,CS/SA,CS/Dex的修饰不仅可以提高GO在生理条件下的分散性和稳定性,而且降低了其非特异性蛋白吸附。2.药物负载实验表明GO-CS-SA和GO-CS-Dex复合物均具有较高的药物负载能力。药物释放实验发现,负载有DOX的GO-CS-SA、GO-CS-Dex复合物展现出明显的p H依赖特性的药物释放行为。通过细胞摄取实验发现两种复合物均易被乳腺癌细胞(MCF-7)摄取,并主要分布在细胞质中。细胞毒性实验表明单纯的GO纳米复合物对细胞没有明显毒性,载药后的纳米复合物对细胞则有显著的细胞毒性作用。3.以GO,PRM和SA为原材料,通过物理吸附作用,使PRM和SA包覆在GO表面。将生成的GO-PRM-SA复合物通过FTIR、AFM、Zeta电位、TGA等表征手段对其进行表征,结果表明PRM和SA成功负载在了GO表面。稳定性试验及非特异性蛋白吸附试验表明,经过PRM/SA修饰的GO不仅可以提高GO在生理条件下的分散性和稳定性,而且降低了其非特异蛋白吸附。将该复合物进行药物负载,结果发现该复合物具有较高的药物负载能力。药物释放实验发现,负载有DOX的复合物展现出明显的p H依赖特性的药物释放行为。最后MTT细胞毒性实验显示负载DOX的GO-PRM-SA对MCF-7细胞具有显著的细胞毒性作用。
[Abstract]:Cancer has been a subject of serious harm to human health. In order to improve the efficiency of cancer and to reduce the side effects of the body in the process of treatment, many drug transport systems have been designed. Among them, the drug transport system mediated by nanomaterials has attracted wide attention. Among the many nanomaterials, GO It is widely used in the field of drug loading because of its water-soluble and superior properties for drug loading. Although graphene oxide has many excellent properties, it is easily aggregated under physiological conditions. Therefore, enhancing its solubility under physiological conditions is the key to understanding the problem. Among them, the surface of GO is carried out. Modification can enhance its solubility under physiological conditions. Layer layer self-assembly technology is an important technique for the surface modification of nanoparticles. It is mainly formed by deposition of polyelectrolytes with opposite charges on the surface of nanoparticles to form a shell nanostructure. However, the layer of charge is stacked with charge on the surface of the graphite oxide nanometallic layer. In this paper, we used two polyelectrolytes with opposite charges, chitosan (CS) and sodium alginate (SA), chitosan (CS) and dextran (Dex), protamine (PRM) and sodium alginate (SA) as membrane materials, using layers self-assembly in this paper. Technology, GO-CS-SA, GO-CS-Dex and GO-PRM-SA nanocomposites were synthesized respectively. Then FTIR, zeta potential and AFM were used to characterize it. Secondly, the stability of the complex and non specific protein adsorption were further studied. Finally, the load of the anti-cancer drug doxorubicin (DOX) was carried out for the nanocomposite, and the drug load and drug were used. The results were as follows: 1. GO was used as the matrix, CS and SA with reverse charge, CS and Dex as polyelectrolytes, and GO-CS-SA and GO-CS-Dex complexes were synthesized by layers self-assembly. FTIR, AFM, Zeta potential and TGA were used to characterize them. The work was coated on the surface of GO. The stability test and the non specific protein adsorption test showed that the modification of CS/SA and CS/Dex could not only improve the dispersion and stability of GO under physiological conditions, but also reduced the non specific protein adsorption.2. drug loading experiment, which showed that both GO-CS-SA and GO-CS-Dex complexes had high drug loading ability. The release experiment showed that the load was DOX GO-CS-SA, and the GO-CS-Dex complex showed a distinct P H dependent drug release behavior. Through the cell uptake experiment, the two compounds were easily absorbed by breast cancer cells (MCF-7) and distributed mainly in the cytoplasm. The cytotoxicity test showed that pure GO nanocomposites were not available to the cells. The nano complex after carrying the drug has significant cytotoxic effect on the cell.3., GO, PRM and SA are used as the raw materials. By physical adsorption, PRM and SA are coated on the surface of GO. The resulting GO-PRM-SA complexes are characterized by FTIR, AFM, Zeta potential, TGA and other characterization methods. On the surface, the stability test and the nonspecific protein adsorption test showed that the PRM/SA modified GO could not only improve the dispersion and stability of GO under physiological conditions, but also reduced the adsorption of nonspecific protein. The compound was loaded with a high drug loading ability. It was found that the complex loaded with DOX showed a distinct P H dependent drug release behavior. Finally, the MTT cell toxicity test showed that the GO-PRM-SA loaded with DOX had significant cytotoxic effect on MCF-7 cells.
【学位授予单位】：江苏大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：TB33;TQ460.1

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