【作者】 刘永；

【导师】 李凤生；

【作者基本信息】 南京理工大学 ， 材料加工工程， 2010， 博士

【摘要】 本文系统地开展了碳纳米管(CNTs)基磁性复合粒子的制备、表面修饰及基础性应用等方面的研究工作。内容涉及纳米Fe3O4/CNTs、CoFe2O4、CNTs、NiFe2O4/CNTs磁性复合粒子的制备、纳米CoFe2O4/CNTs磁性复合粒子的氨基化功能修饰及基于磁靶向热疗和放疗应用的功能化磁性纳米复合粒子的制备及表征,为下一步碳纳米管基磁性复合粒子在肿瘤磁靶向治疗中的应用研究奠定了良好的基础。主要内容如下：首先,分别采用乙二醇溶剂热法及多元醇法制备了梅花状Fe3O4/CNTs磁性复合粒子、亲油性Fe3O4/CNTs磁性复合粒子及单分散性纳米Fe3O4/CNTs、CoFe2O4/CNTs、NiFe2O4/CNTs磁性复合粒子,并通过XRD、TEM、FTIR、XPS. VSM等分析手段对所合成的产物进行了表征。结果表明,采用乙二醇溶剂热法制备的梅花状Fe3O4/CNTs及亲油性Fe3O4/CNTs纳米磁性复合粒子,Fe304纳米粒子如梅花状或类球形被牢固地附着在CNTs表面,且粒径均匀,晶形完好,磁性能测试表明其饱和磁化强度分别达70.7和50.0 emu·g-1,均显示了良好的磁响应性及超顺磁性；采用多元醇法制备的纳米Me2Fe2O4/CNTs(Me=Fe、Co、Ni)磁性复合粒子,包覆层致密均匀,均呈现良好的单分散性、磁响应性及超顺磁性,可以根据实际需要,通过控制反应条件,得到不同包覆密度及磁性能的单分散性纳米Fe3O4/CNTs、CoFe2O4/CNTs、NiFe2O4/CNTs磁性复合粒子,磁性能测试表明在最佳包覆量时其饱和磁化强度分别为30.6、39.5及36.4emu·g-1。其次,对采用不同方法制备的碳纳米管基磁性复合粒子的结构、形貌及磁性能进行了比较和分析。通过对比,选择性能最优的纳米CoFe2O4/CNTs磁性复合粒子作为后续改性实验的载体材料,并采用溶剂-凝胶法以前驱体TEOS作为改性剂对纳米CoFe2O4/CNTs磁性复合粒子表面进行包覆改性,制备出了包覆层厚度均匀可控的具有较强磁响应性的一维纳米SiO2/CoFe2O4/CNTs磁性复合粒子。随后,以γ-氨丙基三甲氧基硅烷(APTES)为氨基化试剂对纳米SiO2/CoFe2O4/CNTs磁性复合粒子进行了进一步的功能化修饰,制备出了表面含有功能基团-NH2的复合载体,并采用XRD、FTIR、VSM等对改性后产物的晶型、结构、组成及磁性能进行了表征与分析。最后,开展了基于磁靶向热疗和放疗应用的基础性初步研究。就磁靶向热疗而言,利用酰胺化反应在氨基化纳米SiO2/CoFe2O4/CNTs磁性复合粒子表面接枝叶酸,利用叶酸受体在癌变组织中高度表达但在绝大多数正常组织中几乎不表达,而叶酸与其受体结合能力强的特点,制备了基于热疗应用的兼具磁靶向与特异性生物靶向的双重靶向药物载体：就磁靶向放疗而言,首先在氨基化纳米SiO2/CoFe2O4/CNTs磁性复合粒子表面固载组氨酸,然后在无水无氧的条件下,合成化合物[N(Et)4][Re(CO)3Br3],将其溶于水后,得到了标记前体化合物普通羰基铼fac-[Re(CO)3(H2O)3]+,最后利用组氨酸含有的咪唑基和普通三羰基铼发生配体反应,开展基于磁靶向放疗应用的普通羰基铼模拟标记实验。采用紫外分光光度计测试吸光度并计算出其模拟标记率达80.85%,标记后其饱和磁化强度值为14.7 emu·g-1,仍保持了较好的磁响应性能,为实现后续放射性核素188Re对固载组氨酸的磁性纳米复合粒子的成功标记提供了理论依据和实验基础。更多还原

【Abstract】 The preparation, surface modification and basic application of carbon nanotubes (CNTs)-based magnetic composite particles were systematically studied in this paper. The research contained the preparation of magnetic nanocomposite particles such as Fe3O4/CNTs、CoFe2O4/CNTs and NiFe2O4/CNTs, the amino functionalization of nano-CoFe2O4/CNTs magnetic composite particles, the preparation and characterization of functional magnetic nanocomposite particles for magnetic targeting hyperthermia and radiotherapy. This work laid a good foundation for the application of CNTs-based magnetic composite particles in magnetic targeted therapy of cancer. The details were described as below:Firstly, the plum-shaped Fe3O4/CNTs, hydrophilic Fe3O4/CNTs and monodispersed Fe3O4/CNTs, CoFe2O4/CNTs, NiFe2O4/CNTs magnetic nanocomposite particles were separately prepared by glycol-solvothermal method and polyol method. The synthesized products were characterized by XRD, TEM, FTIR, XPS, VSM, and so on. The results showed that the plum-shaped Fe3O4/CNTs and lipophilic Fe3O4/CNTs nano-magnetic composite particles which were prepared by ethylene glycol Solvothermal, Fe3O4 nanoparticles were firmly attached on the surface of CNTs like plum-shaped or para-spherical. And the Fe3O4 nanoparticles prepared with uniform size and good crystalline. Magnetic property tests showed that the saturation magnetization reached 70.7 emug-1 and 50.0 emu·g-1, respectively, showing good magnetic responsiveness and superparamagnetism. The Me2Fe2O4/CNTs (Me=Fe、Co、Ni) magnetic nanocomposite particles prepared by polyol method, of which the coating was dense and uniform, had good monodispersibility, strong magnetic responsiveness and superparamagnetism. According to actual needs, monodispersed Fe3O4/CNTs, CoFe2O4/CNTs, NiFe2O4/CNTs magnetic nanocomposite particles with different coating density and magnetic properties were prepared by controlling the reaction conditions. Magnetic property tests showed that the saturation magnetization of them are 30.6,39.5 and 36.4 emu·g-1 at the optimum coating amount, respectively.Secondly, the structures, morphologies and magnetic responsive properties of CNTs-based magnetic nanocomposite particles prepared by different method have been analyzed and compared. By contrast, the result showed that the CoFe2O4/CNTs magnetic nanocomposite particles with the best properties were more fit as a follow-modified carrier material. The one-dimensional SiO2/CoFe2O4/CNTs magnetic nanocomposite particles with uniform and controllable coating layer of SiO2 were prepared by a sol-gel method using TEOS as a precursor modifier. Subsequently, the SiO2/CoFe2O4/CNTs magnetic nanocomposite particles were further functionalized by y-aminopropyl trimethoxysilane (APTES), and then the amino-modified magnetic nanocomposite particles were prepared. The structures, compositions and magnetic properties of modified composite particles were characterized and analyzed by XRD, FTIR, XPS, VSM, et al.Finally, the basic preliminary study based on magnetic targeted hyperthermia and radiotherapy was carried out. On the magnetic targeted hyperthermia, the folic acid was grafted on the surface of amino-modified SiO2/CoFe2O4/CNTs magnetic nanocomposite particles through amidation reaction. The use of folate receptor is highly expressed in cancerous tissue, but in most normal tissues almost no expression, while the dual targeted drug carrier with magnetic target and specifically biological target were prepared; on the magnetic targeted radiotherapy, first of all, the histidine were grafted on the surface of amino-modified SiO2/CoFe2O4/CNTs magnetic nanocomposite particles, then the compound was prepared under anhydrous oxygen-free conditions. When the [N(Et)4][Re(CO)3Br3] was dissolved in the water, the rhenium carbonyl compound precursor fac-[Re(CO)3(H2O)3]+were synthesized. At last, the rhenium carbonyl analog marking experiment based on magnetic targeted radiotherapy were carried out through coordinate reaction between the imidazole group of histidine and general three carbonyl rhenium. The analog marking rate of rhenium calculated by ultraviolet absorbance spectrophotometer was 80.85%, and the saturation magnetization value after marking is 14.7 emu·g-1. The result showed that it remained good magnetic property. The above elementary researches offer the theoretical basis and experimental foundation for the follow-up successful marking of radioactive nuclear 188Re on the magnetic nanocomposite particles which were immobilized by histidine.更多还原