發(fā)布時(shí)間：2018-03-31 23:02

  本文選題：蛋白質(zhì)　切入點(diǎn)：納米金　出處：《北京協(xié)和醫(yī)學(xué)院》2013年博士論文

【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飾,在藥物載體及功能化生物材料構(gòu)建方面已經(jīng)引起廣泛關(guān)注。納米金具有獨(dú)特的理化性質(zhì)及良好的生物相容性,廣泛用于光熱療、成像、傳感器、藥物和基因載體等研究領(lǐng)域。隨著多功能材料越來(lái)越受到重視,雜化材料因其特有的功能在藥物傳遞及其它醫(yī)學(xué)領(lǐng)域顯示出重要的應(yīng)用前景,因此,亟需開展新型有機(jī)-無(wú)機(jī)雜化材料的合成研究。 本論文選用絲素蛋白和牛血清白蛋白(BSA)作為有機(jī)材料,制備成微囊及花狀微結(jié)構(gòu),并用金納米球、納米棒進(jìn)行修飾,從而獲得多功能雜化材料。主要獲得了以下研究結(jié)果或結(jié)論： 1.以絲素蛋白為殼層材料,不引入帶正電的聚電解質(zhì),以PLGA微球?yàn)槟０?用LBL法制備出了一系列不同層數(shù)的絲素蛋白單組分微囊。然后進(jìn)一步制備出兩種雜化微囊：1)殼層夾載金納米棒的雜化微囊；2)表面結(jié)合DNA功能化納米金的雜化微囊。雜化微囊具有控制釋放、聯(lián)合治療、診療一體等多種應(yīng)用潛能。 2.以絲素蛋白為殼層材料,PLGA微球?yàn)槟０?用去溶劑法制備出了絲素蛋白單組分微囊,并通過(guò)金納米球、金納米棒或兩者同時(shí)修飾調(diào)節(jié)微囊的通透性。雜化微囊具有很強(qiáng)的拉曼增強(qiáng)性質(zhì),在診療一體化或光熱療-化療聯(lián)合治療方面具有應(yīng)用潛力。 3.用去溶劑法成功制備了具有特殊拓?fù)浣Y(jié)構(gòu)的BSA花狀微結(jié)構(gòu),每個(gè)結(jié)構(gòu)單元由平行的BSA管狀結(jié)構(gòu)組成；其過(guò)程是蛋白沉積于花狀的無(wú)機(jī)鹽結(jié)晶上形成的；制備了負(fù)載模型藥羅丹明B的BSA花狀微結(jié)構(gòu),作為局部給藥的載體。 4.通過(guò)引入金納米粒子以及RGD對(duì)上述BSA花狀微結(jié)構(gòu)的理化性質(zhì)以及生物活性進(jìn)行調(diào)控。得到的新型雜化材料具有獨(dú)特的力學(xué)性質(zhì)、幾何結(jié)構(gòu)、表面拓?fù)浣Y(jié)構(gòu)以及表面化學(xué)性質(zhì)等,可用于細(xì)胞-材料界面相互作用、局部藥物及細(xì)胞傳遞等的研究。 綜上所述,本研究用LBL、去溶劑法合成了絲素蛋白單組分微囊,再用功能化金納米球和／或金納米棒進(jìn)行修飾,引入的DNA、金納米粒子以及絲素賦予雜化微囊特有的性質(zhì)使其可用于聯(lián)合治療、診療一體化及示蹤等；用去溶劑法制備了BSA花狀微結(jié)構(gòu),并沉積金納米粒子、修飾RGD等。本研究制備的雜化微囊以及雜化花狀微結(jié)構(gòu)為藥物、細(xì)胞傳遞奠定基礎(chǔ)。
[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.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2013
【分類號(hào)】：R318.08
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本文編號(hào)：1692838