蛋白—纳米金杂化微结构在药物载体和生物支架材料中的研究

发布时间：2018-03-31 23:02

  本文选题：蛋白质　切入点：纳米金　出处：《北京协和医学院》2013年博士论文

【摘要】：蛋白基材料具有良好的生物相容性、生物降解性并易于功能化修饰,在药物载体及功能化生物材料构建方面已经引起广泛关注。纳米金具有独特的理化性质及良好的生物相容性,广泛用于光热疗、成像、传感器、药物和基因载体等研究领域。随着多功能材料越来越受到重视,杂化材料因其特有的功能在药物传递及其它医学领域显示出重要的应用前景,因此,亟需开展新型有机-无机杂化材料的合成研究。 本论文选用丝素蛋白和牛血清白蛋白(BSA)作为有机材料,制备成微囊及花状微结构,并用金纳米球、纳米棒进行修饰,从而获得多功能杂化材料。主要获得了以下研究结果或结论： 1.以丝素蛋白为壳层材料,不引入带正电的聚电解质,以PLGA微球为模板,用LBL法制备出了一系列不同层数的丝素蛋白单组分微囊。然后进一步制备出两种杂化微囊：1)壳层夹载金纳米棒的杂化微囊；2)表面结合DNA功能化纳米金的杂化微囊。杂化微囊具有控制释放、联合治疗、诊疗一体等多种应用潜能。 2.以丝素蛋白为壳层材料,PLGA微球为模板,用去溶剂法制备出了丝素蛋白单组分微囊,并通过金纳米球、金纳米棒或两者同时修饰调节微囊的通透性。杂化微囊具有很强的拉曼增强性质,在诊疗一体化或光热疗-化疗联合治疗方面具有应用潜力。 3.用去溶剂法成功制备了具有特殊拓扑结构的BSA花状微结构,每个结构单元由平行的BSA管状结构组成；其过程是蛋白沉积于花状的无机盐结晶上形成的；制备了负载模型药罗丹明B的BSA花状微结构,作为局部给药的载体。 4.通过引入金纳米粒子以及RGD对上述BSA花状微结构的理化性质以及生物活性进行调控。得到的新型杂化材料具有独特的力学性质、几何结构、表面拓扑结构以及表面化学性质等,可用于细胞-材料界面相互作用、局部药物及细胞传递等的研究。 综上所述,本研究用LBL、去溶剂法合成了丝素蛋白单组分微囊,再用功能化金纳米球和／或金纳米棒进行修饰,引入的DNA、金纳米粒子以及丝素赋予杂化微囊特有的性质使其可用于联合治疗、诊疗一体化及示踪等；用去溶剂法制备了BSA花状微结构,并沉积金纳米粒子、修饰RGD等。本研究制备的杂化微囊以及杂化花状微结构为药物、细胞传递奠定基础。
[Abstract]:Protein based materials have good biocompatibility, biodegradability and easy functional modification. Nanocrystalline gold has been widely used in photothermal therapy, imaging and sensors for its unique physical and chemical properties and good biocompatibility. As more and more attention has been paid to multifunctional materials, hybrid materials have shown important application prospects in drug delivery and other medical fields because of their unique functions. It is urgent to study the synthesis of new organic-inorganic hybrid materials. In this paper, silk fibroin and bovine serum albumin (BSA) were used as organic materials to prepare microcapsules and flower-like microstructures, and were modified with gold nanospheres and nanorods. Thus, the multifunctional hybrid materials were obtained. The following results or conclusions were obtained:. 1. Using silk fibroin as shell material, no polyelectrolyte with positive charge and PLGA microspheres as template. A series of silk fibroin monocomponent microcapsules with different layers were prepared by LBL method. Then two hybrid microcapsules containing gold nanorods containing gold nanorods were prepared, and then two hybrid microcapsules with DNA functionalized gold nanoparticles were prepared on the surface of the hybrid microcapsules containing gold nanorods. Hybrid microcapsules have controlled release, Combined therapy, diagnosis and treatment of a variety of potential applications. 2. Silk fibroin mono-component microcapsules were prepared by solvent removal method using fibroin as shell material and PLGA microspheres as template, and the microcapsules were prepared by gold nanospheres. Gold nanorods or both modify and regulate the permeability of microcapsules. Hybrid microcapsules have strong Raman enhancement properties and have potential applications in diagnosis and treatment integration or combination of photothermal therapy and chemotherapy. 3. BSA flower-like microstructures with special topological structure were successfully prepared by solvent removal method. Each structural unit was composed of parallel BSA tubular structures, and the process was formed by deposition of proteins on floral inorganic salt crystallization. The BSA floral structure of Rhodamine B was prepared as the carrier of local administration. 4. Through the introduction of gold nanoparticles and RGD to regulate the physicochemical properties and biological activities of the flower-like microstructures of BSA, the new hybrid materials have unique mechanical properties and geometric structure. The surface topological structure and surface chemical properties can be used in the study of cell-material interface interaction, local drug and cell transmission. To sum up, silk fibroin mono-component microcapsules were synthesized by using LBL-dissolvent method and modified with functionalized gold nanospheres and / or gold nanorods. The introduced DNA, gold nanoparticles and silk fibroin can be used in combination therapy, diagnosis and treatment integration, tracer, etc. The flower-like microstructures of BSA were prepared by solvent removal method, and gold nanoparticles were deposited. Modified RGD et al. the hybrid microcapsules and hybrid floral microstructures were prepared in this study to lay the foundation for drug and cell transmission.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2013
【分类号】：R318.08
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本文编号：1692838