磁性氧化铁纳米材料在肿瘤成像与生物免疫磁分离中的应用

发布时间：2018-03-12 15:35

本文选题：磁性　切入点：氧化铁　出处：《吉林大学》2017年博士论文　论文类型：学位论文

【摘要】：本文以高温热分解方法制备了油溶性氧化铁纳米颗粒,利用配体交换的方法将其转移至水相中,并在纳米颗粒表面引入可进一步修饰的可反应的马来酰胺基团。并针对肿瘤微环境中相关分子谷胱甘肽(GSH)设计构建了具有二硫键结构相连的靶向分子RGD和自身肽的多肽序列Arg-Gly-Asp的多肽分子,通过与纳米颗粒表面马来酰胺基团反应,将多肽分子修饰到纳米颗粒表面,成功制备了GSH响应的纳米分子影像探针。其配体中的二硫键结构可被肿瘤微环境中的相关分子GSH还原形成巯基,并与相邻纳米颗粒上的马来酰亚胺残基反应,导致纳米颗粒交联聚集;我们系统的研究了探针在GSH作用下的诱导聚集行为,并通过对聚集体磁学性质的研究,揭示了氧化铁纳米颗粒的聚集行为与磁共振信号对比度增强效果间的关系;通过小鼠巨噬细胞对探针的摄取来考察探针修饰自身肽后体外逃避免疫延长血液循环时间的能力。随后对探针进行放射性核素标记,制备得到了具有MRI/SPECT双模态分子影像探针,并应用于体内肿瘤检测。体内与体外的MRI成像结果不仅证明了聚集可显著增强分子探针的弛豫性能,而且实现了体内肿瘤的双模态成像。智能响应型探针设计构建的新颖之处在于表面修饰策略,不仅增强MRI造影效果,而且能够逃避免疫吞噬,还可以主动靶向及双模态成像。而后,又设计制备Ca~(2+)诱导Fe_3O_4纳米颗粒聚集制备了聚集体。在表面包被沙门氏菌抗体制备了免疫磁珠,并对沙门氏菌进行分离捕获实验,获得了较好的捕获效率。
[Abstract]:In this paper, oil soluble iron oxide nanoparticles were prepared by high temperature thermal decomposition and transferred to water phase by ligand exchange. Furthermore, a reactionable Maleamide group was introduced on the surface of nanoparticles. The targeted molecule RGD and autopeptide with disulfide bond structure were designed and constructed for glutathione glutathione (GSH) related molecules in tumor microenvironment. Of the polypeptide sequence Arg-Gly-Asp, The polypeptide molecules were modified onto the surface of nanoparticles by reaction with the Maleamide group on the surface of nanoparticles. GSH responsive nanomolecular imaging probe was successfully prepared. The disulfide bond structure in the ligand can be reduced to sulfhydryl group by the related molecule GSH in the tumor microenvironment and react with the Maleimide residue on the adjacent nanoparticles. We systematically studied the induced aggregation behavior of the probes under the action of GSH, and studied the magnetic properties of the aggregates. The relationship between the aggregation behavior of ferric oxide nanoparticles and the contrast enhancement effect of magnetic resonance signal is revealed. The ability of the probe to evade immunity and prolong the blood circulation time was investigated by the uptake of the probe by mouse macrophages. Then the probe was labeled with radionuclide and the MRI/SPECT bimodal molecular imaging probe was prepared. The results of MRI imaging in vivo and in vitro not only proved that aggregation can significantly enhance the relaxation properties of molecular probes, The novel design of intelligent responsive probe is that the surface modification strategy can not only enhance the effect of MRI imaging, but also avoid immune phagocytosis. Then Ca~(2 was designed to induce the aggregation of Fe_3O_4 nanoparticles to produce aggregates. The immunomagnetic beads were prepared by coating the antibodies against Salmonella on the surface, and the isolation and capture experiments of Salmonella were carried out. Better capture efficiency is obtained.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R73-3;TB383.1

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