空心纳米结构材料及其生物医学应用

发布时间：2018-03-28 05:24

本文选题：空心纳米结构　切入点：药物载体　出处：《浙江大学》2015年博士论文

【摘要】：化疗是一种治疗肿瘤的常见临床手段,然而化疗对正常细胞、组织和器官会产生毒副作用。肿瘤对化学药物产生的耐药性会进一步制约了化疗的效果。因此,人们提出基于纳米药物载体提高药物的靶向性及抗肿瘤活性。基于生物安全性的考虑,这些纳米材料不仅具有很好的载药性,还应该拥有良好的生物相容性,特别是进入体内后不容易被识别清除以及在体内的非特异性积累也不会产生严重的副作用。针对以上问题,本论文设计合成一系列多功能纳米药物载体用于肿瘤治疗的应用研究。论文构架如下：第一章我们对空心纳米结构的材料的合成方法及其在生物医学上的应用进行了概述。介绍了几种典型的空心纳米结构的材料作为纳米药物载体在肿瘤治疗方面的应用,并针对目前的纳米药物载体应用的不足之处提出了结合不同治疗方式和提高纳米药物载体靶向性的策略来改善肿瘤的治疗效果,从而引出了本文研究的总体思路和目标等。第二章介绍一种通过以立方体的氧化亚铜与硫脲反应来合成空心的纳米笼结构的硫化铜晶体的方法。合成的纳米笼结构的CuS载体对抗癌药物阿霉素具有非常高的药物负载量,并且药物从载体上的释放过程可以通过pH来控制。由于CuS纳米晶体可吸收近红外光并将其转化为热,可以用于光热治疗肿瘤细胞。因此,CuS纳米载体可以实现化疗和热疗的结合,有效地提高肿瘤细胞的治疗效果。第三章介绍一种具有优异的生物相容性的纺锤形空心聚吡咯的纳米胶囊。这种空心的纳米胶囊可以作为纳米载体用于抗癌药物的运输并可以进一步通过形状控制优化其进入肿瘤细胞的效率。由于聚吡咯可以吸收近红外光并将其转化为热从而通过光热治疗方式灭活肿瘤细胞。因此,聚吡咯纳米胶囊也可以通过结合化疗与热疗实现提高肿瘤治疗效果。第四章我们制备了一种具有yolk-shell结构的Fe3O4@NiSiO3的磁性纳米颗粒,每一个纳米颗粒都是由一个磁性的Fe304的核与具有介孔结构的空心的硅酸镍的壳组成。该纳米结构不仅能够作为高效的药物载体,其外壳表面所富含大量Ni2+可还用于选择性吸附His-标签蛋白用于蛋白的选择性分离和纯化。该材料作为纳米颗粒具有很好的磁响应性,因此外加磁场可以实现材料的循环使用。第五章我们设计了一种yolk-shell结构的Fe3O4@MgSiO3的磁性纳米颗粒,通过表面修饰聚乙二醇高分子和叶酸分子使其不仅具有非常好的生物相容性,而且还可以实现对肿瘤细胞的双靶向(磁靶向和分子靶向)。动物实验表明这种具有双靶向的磁性纳米颗粒能够负载抗癌药阿霉素,改变药物在体内脏器的分布,大幅度提高药物在肿瘤部位的靶向富集,甚至对耐药性肿瘤也具有非常好的治疗效果。第六章我们对本论文的工作进行了总结。合成了一系列的多功能的纳米载体,提出结合不同的治疗方式和改善载体的靶向性的策略来提高肿瘤的治疗效果。取得了十分明显的效果,我们相信这些纳米药物载体在肿瘤肿瘤中会有着巨大的应用前景。
[Abstract]:Chemotherapy is a common clinical method for treating tumor, but chemotherapy on normal cells, tissues and organs will produce toxic side effects of chemical drugs. Drug resistance of tumor will further restrict the chemotherapy effect. Therefore, it is proposed to improve the antitumor activity of nano drug carriers to and drug targets based on biological safety. Based on these nano materials not only has good load resistance, also has a good biocompatibility should be, especially after entering the body is not easy to be identified and cleared accumulation does not cause serious side effects in non specificity in vivo. To solve the above problems, this paper designed and synthesized a series of multifunctional nano drug carrier for the application of tumor therapy. The framework is as follows: the first chapter we materials on synthesis method of hollow nanostructures and their applications in biomedicine were The overview as nano drug carrier hollow nanostructures of several typical materials used in the treatment of cancer, and the combination of different treatment methods and improvement of nano drug carrier targeted strategies to improve the treatment of cancer in view of the deficiency of nano drug carriers used at present is put forward, which leads to the overall the ideas and goals. The second chapter introduces a method of the copper sulfide crystal nano cage structure with cuprous oxide with thiourea to synthesize hollow cube. The CuS vector nano cage structure synthesis of drugs with very high load of anticancer drug doxorubicin, and drug release from the carrier can be controlled by pH. Because CuS nanocrystals can absorb near-infrared light and convert it into heat, can be used for photothermal therapy of tumor cells. Therefore, CuS nanoparticles can be In order to realize the combination of chemotherapy and hyperthermia, effectively improve the treatment effect of tumor cells. The third chapter introduces a nano capsule compatibility of hollow spindle polypyrrole. Excellent bio nano capsule can be used as the hollow nano carrier for anticancer drug transport and can further optimize its efficiency into tumor cells by the shape control because Polypyrrole can absorb NIR light and converted into heat by photothermal treatment of inactivated tumor cells. Therefore, polypyrrole nano capsule can also be realized by combining chemotherapy and hyperthermia treatment of tumors. In the fourth chapter, we prepared high magnetic nanoparticles with a structure of yolk-shell Fe3O4@NiSiO3 were prepared, each nano the particles are composed of nickel silicate a magnetic Fe304 core and mesoporous hollow shell. The nano structure not only Can be used as drug carrier, and the shell surface are rich in a large number of Ni2+ can be also used for selective adsorption of His- tagged protein for protein separation and purification. The selectivity of the material as nano particles have good magnetic response, so the magnetic field can achieve the use of recycled materials. In the fifth chapter, we design a kind of yolk-shell magnetic nanoparticles the structure of the Fe3O4@MgSiO3, through the surface modification of polyethylene glycol polymer and folic acid molecules which not only has excellent biocompatibility, but also can achieve the dual target of tumor cells to (magnetic targeting and molecular targeting). Animal experiments show that the magnetic nanoparticles with dual targeting anticancer drug doxorubicin to load change, the distribution of drugs in the body organs, greatly improve the drug to enrichment at the site of the tumor target, even with very good treatment of tumor drug resistance Results. In the sixth chapter of this paper we summarize the work. A series of multifunctional nanoparticles were synthesized, combining with the treatment and improvement of different carriers for targeted strategies to improve the treatment of cancer. Made very significant results, we believe that there will be a nano drug carrier great application prospect in the tumor.

【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：TB383.1

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