【作者】 王云；

【导师】 丁轶；

【作者基本信息】 山东大学 ， 材料学， 2013， 硕士

【摘要】 磁性纳米颗粒在生物医学领域有很多的应用,其可以作为肿瘤磁感应热疗的介质材料和磁共振成像(MRI)的对比增强剂。本研究立足于将靶向技术用于肿瘤诊疗一体化技术的理论基础,基于磁性纳米介质在研究和临床应用的巨大潜力和优势,提出了以脱氧葡萄糖作为靶向分子。期望将肿瘤靶向技术、磁感应热疗、磁共振成像检测的优势有机融合,达到一种介质、多重功效、靶向治疗的肿瘤靶向诊疗一体化的效果,并为肿瘤磁感应热疗提供功能型热疗介质。研究主要内容如下：1.通过共沉淀法和氧化沉淀法分别合成出纳米四氧化三铁磁性颗粒。利用TEM. XRD和VSM测试对比两种方法制备材料的形貌结构及性能。用共沉淀法制备出的纳米颗粒较小,约为10nm左右,团聚比较严重,饱和磁化强度为68.8emu/g,结晶性不太好。用氧化沉淀法制备出的纳米颗粒粒径较大,在100nm左右,分散性较好,饱和磁化强度为84.5emu/g,结晶性较好。经过充分的对比,从而决定选择用氧化沉淀法制备四氧化三铁磁性纳米颗粒作为后续修饰的磁核材料。2.对四氧化三铁磁颗粒进行二氧化硅的修饰,利用硅源水解方法,合成出核壳型的Fe3O4@SiO2磁性复合材料。通过透射电镜表征其二氧化硅壳层较薄,红外测试结果显示材料含有硅氧键的特征峰,证明成功修饰上二氧化硅并通过VSM测试表明磁性只有微量下降。二氧化硅修饰后提高了材料的稳定性而且使其能更好得修饰上氨基硅烷。进一步利用3-氨丙基三乙氧基硅烷在Fe3O4@SiO2表面引入氨基集团,通过TGA和XPS以及FTIR的测试证明氨基硅烷成功修饰在复合磁颗粒表面,并有自由的氨基集团。之后脱氧葡萄糖聚乙二醇NHS酯通过和磁颗粒上的氨基经过反应形成酰胺键,合成出带有靶向官能团的磁颗粒。通过热重分析和红外测试表明修饰上了脱氧葡萄糖及聚乙二醇,使磁材料具有靶向性和体内的长循环性。3.测试脱氧葡萄糖及聚乙二醇修饰的磁颗粒的磁感应热疗效果,通过对比不同浓度和不同磁场下的升温情况,表明修饰的材料不仅具备升温效果,而且通过改变浓度或者磁感应强度能影响升温情况,从而可以进行温度可控的磁感应热疗。分别测试氧化沉淀法和共沉淀法合成的四氧化三铁颗粒以及脱氧葡萄糖聚乙二醇修饰磁颗粒的MRI的T2成像性能。发现三种材料都具有T2加权成像对比增强效果,氧化沉淀法制备的四氧化三铁颗粒效果最好,其次是修饰后的磁颗粒。对修饰后的复合材料本身进行分析,其中带有的脱氧葡萄糖本身不仅是靶向作用,而可以实现材料在肿瘤细胞的聚集,而其中的四氧化三铁既是肿瘤热疗的介质材料,也可以作为磁共振成像中T2加权的对比增强剂,说明这种材料可以很好得将肿瘤的治疗和诊断结合在一起,实现肿瘤诊疗一体化。更多还原

【Abstract】 The magnetic nanoparticle has various applications in the biomedical field, one of which may be used as the tumor hyperthermia material magnetic induction and magnetic resonance imaging (MRI) contrast enhancer. By applying the targeting technology to the integration technology of tumor clinics as its theoretical foundation, this study tries to take the deoxyglucose as the targeting molecule, which has great potential and advantages in and clinical applications and researches of magnetic nano-based media. The expectations of this study aims at integrating the tumor targeting technology, the magnetic induction hyperthermia therapy, and the magnetic resonance imaging detection. Meanwhile, a series of effect of cancer-targeted therapy can be thus motivated, providing a functional hyperthermia medium as well. The processes of the study are illustrated as follows:1. Fe3O4particles are synthesized by co-precipitation method and oxidation precipitation method. Morphology of the material structure and their properties of these two methods are compared by the TEM, XRD and VSM test. Nano-particles prepared by the former method are smaller (each about10nm or so). They are seriously reunioned, with the saturation magnetization of68.8emu/g, and are not well-crystallized. Nanoparticles prepared by latter method have a larger size (preferably about100nm), which are preferably crystallized and dispersed, with a saturation magnetization of84.5emu/g. After sufficient contrast, the oxidation precipitation method is thus applied in order to prepare Fe3O4nanoparticles as the magnetic nuclear material for the following procedures.2. By modifyng Fe3O4particles with silica, using the hydrolysis method, a synthesis of core-shell Fe3O4@SiO2magnetic material is composed. This silica shell is relatively thin tested through the TEM. A silicon-oxygen bond characteristic peak contained in the material is detected by the FTIR test, proving that the modification of silica is successful. And the VSM test shows that the magnetic of this material is rarely decreased. Meanwhile, the modification improves the stability of the material and so that it can obtain better modifier on aminosilane. In the further step, by introducing the3-aminopropyl triethoxysilane to the surface of the Fe3O4@SiOi, the amino silane is successfully modified on the surface of the composite magnetic particles with the free amino group, according to the TGA. XPS and FT1R test. After deoxy-glucose polyethylene glycol NHS esters react to form an amide bond and the amino group on the magnetic particles after the synthesis of magnetic particles with a target functional group. By thermal gravimetric analysis and infrared testing indicates that the material modification deoxyglucose and polyethylene glycol, the magnetic material has a long cycle of targeting and in vivo.3. This test deoxyglucose and polyethylene glycol-modified magnetic particles magnetic induction hyperthermia effect warming by comparing different concentrations and different magnetic field, shows that the modified materials not only have a warming effect, and can affect the temperature rise by changing the concentration or the magnetic induction intensity. which can be temperature-controlled magnetic induction of hyperthermia. Were tested oxide precipitation and coprecipitation method FC3O4particles and deoxyglucose polyethylene glycol-modificd magnetic particles MRI T2imaging performance. Found that the three materials have the T2-weighted imaging contrast enhancement oxide precipitate prepared Fe3O4particle effects, followed by the modified magnetic particles. Modified composite analysis, with deoxyglucose is not only targeting the accumulation of material in tumor cells can be achieved, and the Fe3O4both hyperthermia dielectric material can also be as T2-weighted magnetic resonance imaging contrast enhancers, this material can be a very good treatment and diagnosis of the tumor together achieve the integration of the cancer clinic.更多还原