无机微纳米材料的仿生合成及其在药物输送和光催化领域的潜在应用

发布时间：2018-08-13 13:39

【摘要】：恶性肿瘤作为临床上最难治愈的疾病之一,严重威胁着全世界人民的生命安全。目前对其常规的疗法仅限于手术治疗、化学治疗和放射治疗,但这些方法存在副作用较大、靶向性低、易产生抗药性等缺点。抗肿瘤靶向制剂的出现,克服了以上常规疗法的不足,可以减小对其他正常组织的毒副作用、降低给药量以及提高药效。无机纳米材料具有诸多优异的物理化学性能,被广泛用于药物输送、荧光标记、锂电池、催化、污水处理、传感和化学储能等。近年来,利用生物矿化机制进行仿生合成是的材料化学领域的热点,但是对于材料的结构、尺寸、形貌和晶型等与其细胞生物学效应之间的关系研究较少。未来应加强在该方向的研究,并在实际应用之前评估其科学性、安全性和有效性,为无机纳米材料的设计合成与其在生物医学领域的应用提供理论依据。本论文主要开展了以下几方面的研究:利用花粉溶出物作为有机基质,合成了多孔空壳碳酸钙材料,通过多种不同手段对样品的形貌和性质进行了测试和表征。结果表明,所合成材料粒径均一,存在大量介孔,且内部为中空结构,具有较大的比表面积,这些性质都有助于提高材料的药物负载能力。以抗肿瘤药物盐酸阿霉素作为模型,对所合成的CaCO3材料进行了体外药物负载-控释实验。实验结果表明,合成的CaCO3材料对药物具有高的负载能力,达到了91.4%。控释实验结果表明,实验合成的CaCO3具有pH敏感性,在弱酸性条件下,能够逐渐分解,继而释放出药物,而它在中性和弱碱性条件下是很难分解的。由此,可减少在正常细胞周围释放。研究表明,所合成的材料可以对抗肿瘤药物进行持续可控释放,延长药物的释放时间,减少给药次数,这一结果也为材料的细胞活性实验提供了重要的依据。细胞生物学测试结果显示,将DOX负载于材料后,药物的特异性显著增加,可提高至纯药的17倍。体外细胞实验证实,合成的多孔空壳碳酸钙可以通过胞吞作用进入肿瘤细胞内部,进而释放出药物。综上所述,实验合成的多孔空壳碳酸钙在抗肿瘤药物负载和临床肿瘤治疗领域有着广阔的潜在应用前景。用液-液界面反应的简便方法合成了立方双层壳碳酸钙和立方空壳碳酸钙,本文探究了其反应物浓度和反应温度对其形貌的影响。文中用场发射扫描电镜、透射电镜等对其进行表征,并对其形成机理进行初步推测。用溶剂热法合成了具有介孔结构的花状硫化铜。测试结果表明,实验合成的CuS形貌大小均一,由数十片薄片组成,粒径约为340 nm。该片组装花状CuS半导体材料具有优异的光学性能,其间接半导体和直接半导体禁带宽度分别为1.36 eV、2.14 eV。因其具有较大的比表面积和孔容,使得样品表面存在更多的活性位点,在催化反应中表现出优异的光催化活性,这使其在催化领域具有广阔的潜在应用前景。该研究以亚甲基蓝为有机污染物模型,实验结果为其进一步用于降解其他有机毒性污染物提供了实验依据及理论指导。
[Abstract]:As one of the most difficult diseases to cure in clinic, malignant tumors seriously threaten the lives of people all over the world. At present, the conventional therapy is limited to surgical treatment, chemotherapy and radiotherapy, but these methods have some disadvantages, such as large side effects, low targeting, easy to produce drug resistance and so on. Inorganic nanomaterials have many excellent physical and chemical properties and are widely used in drug delivery, fluorescence labeling, lithium batteries, catalysis, sewage treatment, sensing and chemical energy storage. In recent years, biomineralization mechanisms have been used to improve the performance of inorganic nanomaterials. Biomimetic synthesis is a hotspot in the field of material chemistry, but little research has been done on the relationship between the structure, size, morphology and crystal form of materials and their cellular biological effects. In this paper, the porous and hollow calcium carbonate materials were synthesized by using pollen extract as organic matrix. The morphology and properties of the samples were tested and characterized by various means. The results showed that the synthesized materials had uniform particle size and existed. A large number of mesoporous materials with hollow structure and large specific surface area can improve the drug loading ability of the materials. The drug loading-controlled release experiments of the synthesized CaCO3 materials were carried out in vitro with the antitumor drug adriamycin hydrochloride as the model. The results showed that the synthesized CaCO3 materials had high drug loading-controlled release ability. The results of controlled-release experiments showed that the CaCO3 synthesized in this experiment was pH-sensitive and could decompose gradually under weak acidic conditions, and then release the drug. However, it was difficult to decompose under neutral and weak alkaline conditions. Thus, the release around normal cells could be reduced. The results of cytobiological assay showed that the specificity of the drug was significantly increased when DOX was loaded on the material, which was 17 times higher than that of the pure drug. In summary, the experimental synthesis of porous calcium carbonate has broad potential applications in the fields of antitumor drug loading and clinical tumor therapy. Cubic bicapsular carbonate was synthesized by a simple method of liquid-liquid interface reaction. Calcium and cubic hollow calcium carbonate were characterized by field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM). Flower copper sulfide with mesoporous structure was synthesized by solvothermal method. The fabricated flower-like CuS semiconductors have excellent optical properties. The band gap of indirect and direct semiconductors are 1.36 eV and 2.14 eV, respectively. Because of their large specific surface area and pore volume, more active sites are found on the surface of the sample. The photocatalytic activity of methylene blue is excellent, which makes it have a broad potential application in the catalytic field. Methylene blue is used as organic pollutant model in this study. The experimental results provide experimental basis and theoretical guidance for its further application in the degradation of other organic toxic pollutants.
【学位授予单位】：河南师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：TB383.1

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