二氧化铈基纳米材料的抗氧化机理及生物应用研究

发布时间：2019-05-17 15:04

【摘要】：研究表明氧化应激与多种疾病的产生密切相关,它是由于活性氧物种在生物体内的过量积累而导致的。因此,抗氧化剂在氧化应激相关疾病的治疗中具有重要的应用价值。具有氧化还原性质的纳米材料因结构稳定、活性可再生等优点在生物抗氧化领域备受关注。其中,二氧化铈(CeO_2)纳米材料因优异的氧化还原能力在生物抗氧化领域应用最为广泛。本论文围绕CeO_2纳米材料的合成、抗氧化机理研究、抗氧化活性调控、及生物应用研究进行展开。CeO_2中Ce3+与Ce4+可相互转换,这一转换过程伴随着氧缺陷的生成与消除。近些年,CeO_2纳米材料因这一可逆的变价性质及良好的生物安全性成为备受关注的生物抗氧化材料。研究表明CeO_2纳米材料可消除生物体内过量的活性氧物种,进而在多种疾病产生过程中体现出抗氧化保护或疾病治疗的作用。但是其抗氧化机理仍不清晰、抗氧化活性的调控及多功能化修饰的研究仍较缺乏、抗氧化生物应用仍需进一步的研究拓展。本文基于CeO_2纳米材料抗氧化过程中物理化学性质的变化,并结合定性的光谱表征及定量的催化实验探究其抗氧化机理。在此基础上,本文进一步研究了CeO_2纳米材料抗氧化活性的调控及其在胰岛b细胞中的抗氧化保护作用。此外,本文还实现了具备抗氧化性、核磁共振造影成像及CT造影成像的多功能CeO_2基纳米材料的合成及性质研究。本文的研究重点围绕以下两方面进行展开:(1)CeO_2纳米材料的抗氧机理研究及抗氧化活性调控通过紫外可见吸收光谱、X射线吸收谱、拉曼光谱等原位表征技术,探测CeO_2抗氧化反应过程中Ce的价态、局域配位环境及吸附氧物种等的变化。实验结果表明:CeO_2与H_2O_2反应后吸收光谱发生红移;CeO_2中铈离子的配位数呈现先增大后减小至初始值的趋势。结合定量的催化实验结果表明:CeO_2的抗氧化能力取决于与过氧物种配位的Ce位点的氧化还原能力,且在CeO_2循环催化H_2O_2分解过程中,Ce4+被还原一步是抗氧化反应的关键步骤。这一研究深入理解并揭示了CeO_2的抗氧化机理。基于抗氧化机理的研究,我们采用稀土Gd3+离子掺杂的手段调控了CeO_2纳米材料的氧缺陷状态,进而提高了CeO_2的抗氧化活性,并且这一活性的提高在催化循环及细胞环境中仍可保持。此外,调控机理研究表明掺杂能提高CeO_2与氧物种的配位能力及表面Ce位点的氧化还原性,进而提高了其抗氧化活性。(2)CeO_2基纳米材料的多功能化研究及生物应用探索本文将高温热分解法制备的CeO_2:Gd纳米花经转水相修饰上亲水性配体,并系统研究了其抗氧化性、MRI造影成像及CT造影成像性质。此多功能纳米材料可潜在应用于CeO_2纳米材料活体治疗应用时的示踪及临床指导。本文成功建立了H_2O_2、高糖及链脲佐菌素(STZ)诱导的INS-1细胞凋亡模型,并探索了CeO_2纳米材料在这三种细胞凋亡模型中的保护作用。实验结果表明所制备CeO_2纳米颗粒在INS-1细胞中生物相容性良好,且可抑制H_2O_2导致的细胞凋亡。本文还探索了CeO_2纳米材料在增强阿霉素对白血病耐药细胞(HL-60耐药细胞)的治疗作用方面的应用。
[Abstract]:Studies have shown that oxidative stress is closely related to the production of a variety of diseases, which is due to the excessive accumulation of active oxygen species in the organism. Therefore, the antioxidant has important application value in the treatment of oxidative stress-related diseases. The nano material has the advantages of stable structure, and renewable activity and the like, and is of great concern in the field of biological oxidation. Among these, CeO _ 2 nano-materials are the most widely used in the field of bio-oxidation. In this paper, the synthesis of CeO _ 2 nano-material, the research of anti-oxidation mechanism, the control of anti-oxidation activity and the research of biological application were carried out. Ce3 + and Ce4 + in CeO _ 2 can be converted to each other, and the conversion process is accompanied with the generation and elimination of oxygen defects. In recent years, CeO _ 2 nano-material has become an important biological and antioxidant material because of this reversible price-changing property and good biological safety. The research shows that the CeO _ 2 nano-material can eliminate the excess active oxygen species in the living body, and then the effect of antioxidant protection or disease treatment can be reflected in the production of various diseases. However, the anti-oxidation mechanism is still unclear, the control of the anti-oxidation activity and the research of the multi-function modification are still short, and the anti-oxidation biological application still needs further research and development. Based on the change of physical and chemical properties in the oxidation process of CeO _ 2 nano-materials, the anti-oxidation mechanism of CeO _ 2 nano-material is investigated by means of qualitative and quantitative catalytic experiments. On this basis, the anti-oxidation activity of CeO _ 2 nano-material and its anti-oxidation protection in the islet b cells were studied. In addition, the synthesis and properties of a multifunctional CeO _ 2-based nano-material with oxidation resistance, magnetic resonance imaging and CT contrast imaging are also realized. The research focused on the following two aspects: (1) the research of the anti-oxygen mechanism of CeO _ 2 nano-material and the control of oxidation-resistant activity by the in-situ characterization technology such as ultraviolet-visible absorption spectrum, X-ray absorption spectrum, Raman spectrum and the like, and the valence state of Ce in the process of oxidation reaction of CeO _ 2 is detected. And the change of the local coordination environment and the adsorbed oxygen species. The results show that the absorption spectrum of CeO _ 2 and H _ 2O _ 2 is red shift, and the coordination number of the ions in CeO _ 2 is first increased and then decreases to the initial value. The experimental results show that the oxidation resistance of CeO _ 2 depends on the oxidation-reduction ability of the Ce site in coordination with the peroxy species, and the reduction of Ce4 + is a key step in the oxidation reaction during the decomposition of the H _ 2O _ 2 by the CeO _ 2 cycle. This study deeply understands and reveals the oxidation mechanism of CeO _ 2. Based on the research of the anti-oxidation mechanism, we use the rare-earth Gd3 + ion doping to control the oxygen-deficient state of CeO _ 2 nano-material, and then increase the anti-oxidation activity of CeO _ 2, and the increase of this activity can still be maintained in the catalytic cycle and the cell environment. In addition, the study of regulation mechanism shows that the doping can improve the coordination ability of CeO _ 2 and the oxygen species and the oxidation and reduction of the surface Ce sites, and further improve the anti-oxidation activity of the CeO _ 2 and the oxygen species. (2) The study on the multi-function of CeO _ 2-based nano-materials and the application of biological applications to the preparation of CeO _ 2: Gd nanoparticles by high-temperature thermal decomposition method were studied. The anti-oxidation, MRI and CT imaging properties of CeO _ 2: Gd _ 2-based nano-materials were studied. The multifunctional nano-material can be applied to the tracing and clinical guidance of the CeO _ 2 nano-material in-vivo therapeutic application. In this paper, the apoptosis model of the INS-1 cells induced by H _ 2O _ 2, high-glucose and chain-and-chain, and the protective effect of CeO _ 2 nano-materials in these three cell apoptosis models were studied. The results show that the prepared CeO _ 2 nanoparticles have good biocompatibility in the INS-1 cells and can inhibit the apoptosis of the cells induced by H _ 2O _ 2. The application of CeO _ 2 nano-material in the treatment of leukemia-resistant cells (HL-60-resistant cells) was also discussed.
【学位授予单位】：华中科技大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：TB383.1

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