pH敏感型磁性二氧化硅纳米材料的制备及其性能研究

发布时间：2018-11-10 17:32

【摘要】：近些年来生物靶向药物治疗在癌症治疗体系中受到越来越多的关注。它主要是利用纳米材料的靶向运输功能将药物输送到病灶部位,在提高治疗效果的同时还可以减少药物对人体的毒害作用。研究发现病变组织细胞和正常组织细胞存活于不同的生理环境中,主要表现在其微环境的pH值不同。因此,利用pH响应性进行药物缓释逐渐成为了研究的热点。本文以生物相亲性较好的磁性二氧化硅作为基体材料,分别制备出了分散较好,粒径均匀的实心型和介孔型pH响应的纳米药物载体,并对这两种体系的载药性能进行了研究和分析。主要研究内容如下:1.分别采用了水热法和共沉淀法制备出了表面带有不同官能团的Fe_3O_4磁性纳米粒子。水热法制备出的纳米粒子分散性较好,表现出较好的亲水性。共沉淀法制备的纳米粒子分散性相对较差,表现出较好的亲油性。所有纳米粒子都具有合适的粒径和良好的磁响应。综合考虑采用粒径较小的油性Fe_3O_4磁性纳米粒子作为后续反应磁核。2.实验采用微乳液法制备出二氧化硅包覆的Fe3O4磁性纳米复合粒子(Fe_3O_4@SiO_2)。通过硅烷偶联剂的修饰,以及一系列的有机反应,使复合粒子表面带有大量的酰肼键,能够和药物形成pH敏感性的腙键。此方法制备的磁性纳米复合粒子粒径大约在100 nm左右,具有较好的磁响应性和较低的细胞毒性,可以作为合适的靶向药物载体。3.实验采用微乳液法制备出介孔二氧化硅包覆的Fe_3O_4磁性介孔纳米材料(Fe3O4@mSiO_2)。随后在表面包覆上勃姆石(AlOOH),通过原位生长的方式,用硝酸铵作为沉淀剂,在介孔材料表面形成上pH敏感性的双金属氢氧化物(LDH)。所制备出的载药体系粒径大约为100 nm左右,且具有较好的磁响应性和较低的细胞毒性,也可以作为合适的药物载体。4.阿霉素通过和载体形成腙键负载在了载体上,甲氨蝶呤则通过分子运动和离子交换作用储存在二氧化硅的孔洞和LDH的片层之中,形成pH敏感型磁靶向载药体系。实验结果表明:两种载药体系都能够负载上适量的抗癌药物,同时还表现出了较好的pH敏感性和磁靶向性,能有效的杀死肿瘤细胞,达到治疗癌症的作用。
[Abstract]:In recent years, biologically targeted drug therapy has attracted more and more attention in cancer treatment system. It mainly uses the target transport function of nanomaterials to transport drugs to the foci, which can not only improve the therapeutic effect but also reduce the toxic effect of drugs on human body. It was found that pathological tissue cells and normal tissue cells survived in different physiological environments, mainly due to their different pH values in microenvironment. Therefore, the use of pH responsiveness drug delivery has gradually become the focus of research. In this paper, the magnetic silica with good biological affinity was used as the matrix material to prepare nano-drug carriers with good dispersion and uniform particle size of solid type and mesoporous pH response, respectively. The drug loading properties of the two systems were studied and analyzed. The main contents are as follows: 1. Fe_3O_4 magnetic nanoparticles with different functional groups were prepared by hydrothermal method and co-precipitation method respectively. The nanoparticles prepared by hydrothermal method have good dispersion and good hydrophilicity. The dispersion of nanoparticles prepared by coprecipitation method is relatively poor, showing a good lipophilicity. All nanoparticles have appropriate particle size and good magnetic response. The oil Fe_3O_4 magnetic nanoparticles with small particle size are considered as the subsequent reaction magnetic nuclei. 2. 2. Silica coated Fe3O4 magnetic nanoparticles (Fe_3O_4@SiO_2) were prepared by microemulsion method. Through the modification of silane coupling agent and a series of organic reactions, a large number of hydrazide bonds were found on the surface of the composite particles, which could form a Hydrazone bond sensitive to pH with the drug. The magnetic nanoparticles prepared by this method have a good magnetic response and low cytotoxicity, and can be used as a suitable drug carrier for targeting. Fe_3O_4 magnetic mesoporous nanomaterials (Fe3O4@mSiO_2) coated with mesoporous silica were prepared by microemulsion method. Then the surface of the mesoporous material was coated with Boehmite (AlOOH), by in situ growth and ammonium nitrate was used as precipitant to form pH sensitive bimetallic hydroxide (LDH). On the surface of mesoporous materials. The prepared drug carrier system has a particle size of about 100 nm, and has good magnetic response and low cytotoxicity, and can also be used as a suitable drug carrier. 4. Doxorubicin was loaded on the carrier by forming Hydrazone bond with the carrier. Methotrexate was stored in the pore of silica and in the lamellar of LDH through molecular movement and ion exchange to form a pH sensitive magnetic targeting drug system. The experimental results showed that both of the two drug loading systems could load appropriate amount of anticancer drugs, and at the same time showed good pH sensitivity and magnetic targeting, which could effectively kill tumor cells and achieve the effect of cancer treatment.
【学位授予单位】：南京理工大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：TB383.1;TQ460.1

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