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磁性、熒光、CT造影納米微粒的制備、表征及應(yīng)用

發(fā)布時(shí)間:2018-09-14 11:37
【摘要】:納米復(fù)合微粒,尤其是功能性納米復(fù)合微粒近年來(lái)研究廣泛。其中將具有磁性的無(wú)機(jī)材料(如Fe3O4, γ-Fe2O3, Ni, Co以及Mn的氧化物等)與各種具有功能性的聚合物材料(如環(huán)境響應(yīng)性,熒光,靶向治療等)相結(jié)合制備的磁性納米復(fù)合微粒,由于其多樣的功能性,廣泛應(yīng)用于生物醫(yī)藥(如靶向載藥,蛋白質(zhì)、基因、細(xì)胞分離,MRI、CT、光學(xué)造影成像)和工業(yè)應(yīng)用(污水處理等)等領(lǐng)域,均取得了很好的效果,因而其研究潛力巨大。本文通過(guò)使用配體交換法和無(wú)皂乳液聚合法分別制備了具有磁性熒光功能的納米粒子和具有磁性、熒光、CT三重功能的高分子微球。配體交換法是用新合成的配體,在一定條件下置換原有材料表面配體的一類(lèi)方法,在制備水性Fe304納米粒子上應(yīng)用廣泛;無(wú)皂乳液聚合用于合成生物醫(yī)用高分子微球,由于反應(yīng)溫和,沒(méi)有乳化劑的加入,擁有明顯的優(yōu)勢(shì)。其具體內(nèi)容如下:使用3-(甲基丙烯酰氧)丙基三甲氧基硅烷(KH-570),聚乙二醇甲基丙烯酸酯(PEGMA)以及可聚合的熒光配合物Eu(AA)3Phen合成出含稀土Eu元素的兩親性聚合物,然后以其作為配體,以油酸改性的Fe3O4粒子為核,通過(guò)配體交換法,制備出水性磁性熒光微粒。通過(guò)核磁共振波譜儀、傅里葉紅外光譜儀、透射電子顯微鏡、動(dòng)態(tài)光散射粒徑測(cè)試儀、X射線衍射儀、振動(dòng)樣品磁強(qiáng)計(jì)、熒光分光光度計(jì)、熱重分析儀對(duì)該磁性熒光微粒的形態(tài)特征、磁性能和熒光性能等進(jìn)行了測(cè)試表征。所獲結(jié)果表明,制得的兩親性聚合物有效地包覆于磁性納米粒子表面,最終產(chǎn)物磁性熒光微粒能夠良好的分散于水相之中,且粒徑均一,平均粒徑僅45nm。磁性熒光微粒粉末室溫下飽和磁化強(qiáng)度值是2.3 emu/g,熒光性能測(cè)試可得到微粒中稀土Eu3+在594 nm和619 nm位置的明顯特征發(fā)射峰。實(shí)驗(yàn)室制備了新型含碘稀土配合物Eu(AA)2(DTA)Phen,并與Fe304磁流體、苯乙烯(St)以及甲基丙烯酸縮水甘油酯(GMA)結(jié)合起來(lái),通過(guò)無(wú)皂乳液聚合法,制備了以Fe304為磁性中心的雙層核-殼結(jié)構(gòu)聚合物微球。新型含碘配合物具有優(yōu)異的X射線造影和稀土熒光特性,相比于原料中的碘劑,配合物具有了更好的造影效果。結(jié)合了具有雙重功能的配合物與超順磁性Fe304納米粒子制得的磁性功能微球可以應(yīng)用于電子計(jì)算機(jī)斷層掃描(CT),磁共振成像(MRI)以及光學(xué)三重功能造影成像,并表現(xiàn)出許多優(yōu)良的特征:微球表現(xiàn)出良好的均勻分散性且具有很高的封裝率;在體外CT試驗(yàn)中,當(dāng)?shù)庳?fù)載量低于4.8 mgI/ml微球仍然可以表現(xiàn)出明顯的CT造影效果;微球的飽和磁化強(qiáng)度為2.16 emu/g,弛豫率為259.59 mM-1 S-1,其通過(guò)靜脈注射至小鼠體內(nèi)后,在肝臟和脾臟部位表達(dá)出良好的T2造影效果;在雙光子共聚焦成像下,微球在肝臟和脾臟組織中表現(xiàn)出明顯特征紅色熒光。同時(shí),新型的配合物和功能微球也顯示出一種新的碘造影劑試驗(yàn)方法,具有潛在的研究前景。
[Abstract]:Nano-composite particles, especially functional nano-composite particles, have been widely studied in recent years. Magnetic nanoparticles were prepared by combining magnetic inorganic materials (such as Fe3O4, 緯 -Fe _ 2O _ 3, Ni, Co and Mn oxides, etc.) with various functional polymer materials (such as environmental responsiveness, fluorescence, targeted therapy, etc.). Because of its various functions, it has been widely used in biomedicine (such as targeted drug, protein, gene, cell separation MRI CTT, optical imaging) and industrial application (sewage treatment, etc.). Therefore, its research potential is huge. In this paper, nanoparticles with magnetic fluorescence function and polymer microspheres with magnetic and fluorescent CT triple function were prepared by ligand exchange method and soap-free emulsion polymerization method, respectively. Ligands exchange method is a kind of method to replace the surface ligands of the original materials with new synthesized ligands under certain conditions. It is widely used in the preparation of waterborne Fe304 nanoparticles, and soap-free emulsion polymerization is used to synthesize biomedical polymer microspheres. Due to the mild reaction, there is no emulsifier added, with obvious advantages. The main contents are as follows: using 3- (methacryloxy) propyltrimethoxysilane (KH-570), polyethylene glycol methacrylate (PEGMA) and polymerizable fluorescent complex Eu (AA) 3Phen, amphiphilic polymers containing rare earth elements Eu were synthesized and used as ligands. Waterborne magnetic fluorescent particles were prepared by ligand exchange using oleic acid modified Fe3O4 particles as nucleus. By means of nuclear magnetic resonance spectrometer, Fourier infrared spectrometer, transmission electron microscope, dynamic light scattering particle size tester and X-ray diffractometer, vibrating sample magnetometer, fluorescence spectrophotometer, The morphology, magnetic properties and fluorescence properties of the magnetic fluorescent particles were characterized by thermogravimetric analysis. The results show that the amphiphilic polymer is effectively coated on the surface of magnetic nanoparticles, and the final product magnetic fluorescent particles can be well dispersed in the aqueous phase, and the particle size is uniform, the average particle size is only 45 nm. The characteristic emission peaks of rare earth Eu3 at 594 nm and 619 nm can be obtained by measuring the saturation magnetization intensity of the powder at room temperature and measuring the fluorescence properties of the particles at 2. 3 emu/g,. A new iodized rare earth complex, Eu (AA) _ 2 (DTA) Phen, was prepared by soap-free emulsion polymerization with Fe304 magnetic fluid, styrene (St) and glycidyl methacrylate (GMA). Double layer core-shell polymer microspheres with Fe304 as magnetic center were prepared. The new iodized complexes have excellent X-ray radiography and rare earth fluorescence properties, compared with the iodine agent in raw materials, the complexes have a better contrast effect. The magnetic functional microspheres prepared by combining double functional complexes with superparamagnetic Fe304 nanoparticles can be used in (MRI) imaging of (CT), and triple function optical imaging. The microspheres showed good uniform dispersion and high encapsulation efficiency, in vitro CT test, when the iodine loading was less than 4.8 mgI/ml, the microspheres still showed obvious CT imaging effect. The saturation magnetization of the microspheres was 2.16 emu/g, and the relaxation rate was 259.59 mM-1 S-1.After intravenous injection into mice, the microspheres showed a good T 2 imaging effect in the liver and spleen. The microspheres showed obvious red fluorescence in liver and spleen. At the same time, new complexes and functional microspheres also show a new iodine contrast agent test method, which has potential research prospects.
【學(xué)位授予單位】:湖北大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2015
【分類(lèi)號(hào)】:TB383.1

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