氨基化磁性复合物在靶药载体和曼尼希反应中的应用

发布时间：2018-08-03 08:12

【摘要】：氨基化磁性复合纳米材料在催化、传感器、水净化、酶固定、DNA提取及靶向药物载体等领域具有广泛的应用价值,已引起科研人员的关注。本文中,我们采用醇还原法制备Fe304纳米球。从反应时间、乙二醇与水体积比、pH值及溶剂极性等因素探讨Fe304的合成机理。将Fe304质子化,吸附吡咯单体,超声辅助下原位聚合反应制备Fe3O4/PPy复合纳米球。此外,运用共沉淀法制备Fe304纳米颗粒,加入表面活性剂,以苯胺或吡咯为单体,合成氨基化磁性复合物(Fe3O4/PANI、 Fe304/PPy)。采用X-射线粉末衍射(XRD)、傅里叶变换红外光谱(FT-IR)、透射电子显微镜(TEM)、扫描电子显微镜(SEM、Zeta电位、热重差热分析仪(TGA/DSC)及超导量子干涉磁强计(SQIM)技术对样品进行表征。结果表明：(1)上述氨基化磁性复合物具有磁响应性高、水分散性好、超顺磁性等特点。(2)核-壳式结构的Fe3O4/PPy纳米球粒径100 nm,满足生物体内应用要求。将脱掺杂的Fe3O4/PPy纳米球作为药物载体,分别采用静电吸附、EDC/NHS耦合反应接枝异硫氰酸荧光素(FITC)和甲氨蝶呤(MTX)。模拟生物体内环境探究Fe3O4/PPy/FITC/MTX药物释放行为。对Fe3O4、Fe3O4/PPy、Fe3O4/PPy/FITC及Fe3O4/PPy/FITC/MT进行细胞毒性测试。结果表明：(1)Fe3O4/PPy/FITC/MTX载药量109μg/mg。(2)在生理环境下,磁性靶向药物具有良好的药物缓释效应。(3) Fe3O4、Fe3O4/PPy、Fe3O4/PPy/FITC具有生物相容性,Fe3O4/PPy/FITC/MTX对过度表达叶酸受休的Hela细胞具有良好的抑制、杀灭功效。通过对羟基苯甲醛与氨基化磁性复合物耦合反应,采用紫外-可见吸收光谱(UV-Vis)确定复合物表面氨基含量。以Fe3O4/PANI、Fe3O4/PPy为固体胺,与对羟基苯甲醛、乙酰胺基丙二酸二乙酯经过曼尼希反应制备酪氨酸样品。结果表明：(1)氨基化磁性复合物Fe3O4/PANI、Fe3O4/PPy表面氨基含量分别为246.1μmol/g、300.1μmol/g。(2)通过紫外-可见吸收光谱与核磁共振氢谱判定所制备的样品为酪氨酸。(3)此方法可以回收固体胺,重复利用,降低生产成本,保护环境。
[Abstract]:Amino-magnetic composite nanomaterials have wide application value in the fields of catalysis, sensor, water purification, enzyme immobilized DNA extraction and targeted drug carrier, which have attracted the attention of researchers. In this paper, Fe304 nanospheres were prepared by alcohol reduction method. The synthesis mechanism of Fe304 was discussed from the factors of reaction time, pH value of ethylene glycol to water volume ratio and solvent polarity. Fe3O4/PPy composite nanospheres were prepared by in situ polymerization of Fe304, adsorption of pyrrole monomer and in situ polymerization assisted by ultrasound. In addition, Fe304 nanoparticles were prepared by coprecipitation method, and surfactant was added to synthesize magnetic complex (Fe _ 3O _ 4 / PANI, Fe304/PPy) with aniline or pyrrole as monomers. The samples were characterized by X-ray powder diffraction (XRD),) Fourier transform infrared spectroscopy (FT-IR), transmission electron microscope (TEM),) scanning electron microscope (TEM), thermogravimetric differential thermal analyzer (TGA/DSC) and superconducting quantum interference magnetometer (SQIM). The results showed that: (1) the above amino magnetic complexes had the characteristics of high magnetic response, good water dispersion and superparamagnetism. (2) the core-shell structure Fe3O4/PPy nanospheres were 100nm in diameter, which met the requirements of biological application in vivo. The dedoped Fe3O4/PPy nanospheres were used as drug carriers, and the coupling reaction of EDCR / NHS was used to graft fluorescein isothiocyanate (FITC) and methotrexate (MTX).), respectively. To explore the drug release behavior of Fe3O4/PPy/FITC/MTX in vivo. Cytotoxicity tests were performed on Fe3O4 / Fe3O4 / PPyFe3O4 / PPy-FITC and Fe3O4/PPy/FITC/MT. The results showed that: (1) the drug load of Fe3O4/PPy/FITC/MTX was 109 渭 g / mg 路(2) in physiological environment, the magnetic targeted drug had a good sustained release effect. (3) Fe3O4Fe3O4 / PPyFe3O4 / PPy-FITC- FITC had a good biocompatibility to inhibit the overexpression of folic acid in Hela cells. The surface amino content of p-hydroxybenzaldehyde was determined by UV-Vis absorption spectrum (UV-Vis) through coupling reaction between p-hydroxybenzaldehyde and amino-magnetic complex. The samples of tyrosine were prepared by Mannich reaction with p-hydroxybenzaldehyde and diethyl acetamide malonate with Fe _ 3O _ 4 / Pani _ 3O _ 4 / PPy as solid amines. The results showed that: (1) the amino content of Fe _ 3O _ 4 / PANIO _ 4 / PPy surface was 246.1 渭 mol / g ~ (-1) 渭 mol ~ (-1) 路g ~ (-1) respectively. (2) the samples were identified as tyrosine by UV-Vis absorption spectra and hydrogen NMR spectra. (3) solid amines could be recovered and reused by this method. Reduce production costs and protect the environment.
【学位授予单位】：齐鲁工业大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：TB33;TQ460.1

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