二氧化铈纳米晶的晶面调控合成及其抗DNA氧化性能研究

Recently, cerium oxide (CeO2) nanoctrystals have been considered as excellent antioxidants due to the presence of a mixed valence state (Ce3+/4+) at the surface of the nanocrystals, which also attract many attentions in the biological medicine field. However, there are many conflictive studies about the antioxidant activity of CeO2，that was due to the different morphology of CeO2 nanocrystals and experiment conditions were used in those studies, which hamper the comparison of different studies on the biological effects of nanoceria, and also made it not well understand of the antioxidant activity mechanism of CeO2 nanocrystals. All of that greatly restrict the process on the clinic applications of CeO2 nanocrystals. In order to resolve those problems, CeO2 nanocrystals with different crystallite planes will be controlled synthesis and used to explore the effects on the antioxidant activity by DNA protection. The kinds and ratio of displayed crystallite planes, the charge and distribution of surface elements and the concentration of CeO2 nanocrystals will be studied, in order to develop the relations between the displayed crystallite planes of CeO2 crystal and the antioxidant activity on DNA. Due to their small size, nanoparticles exhibit high surface to volume ratio which would lead them to have a high capacity to absorb molecules such as amino acids, proteins, sugars or salts present with in biological media. So，the roles of environments ( pH, kinds and concentration of ion in the buffer, proteins, amino acid and saccharides) and the size effect on the antioxidant activity of DNA damage will also be explored, which will help to understand the relations between the displayed crystallite planes of CeO2 nanocrystal and the antioxidant activity on DNA. With all the experiments, the relations between the kinds and ratio of displayed crystallite planes of CeO2 nanocrystal and the antioxidant activity on DNA will be developed, which would promote the understand of the mechanism of the antioxidant activity on DNA, and will also provide the theoretical and experimental support on CeO2 nanocrystal's applications in the prevention and control of DNA damage related major diseases.

二氧化铈纳米晶由于表面Ce3+/4+的存在而具有独特的抗氧化能力，使其在生物医药领域的应用引起了很大的关注。但是，目前对二氧化铈纳米晶抗氧化性能的研究存在很多矛盾的结论，这主要是由于研究所用的二氧化铈纳米晶形貌各异，并且实验条件各不相同，从而导致实验结果无法比较，也使得对纳米晶抗氧化机理认识不够，从而极大的限制了其临床应用的进展。本课题拟从裸露不同晶面的二氧化铈纳米晶可控制备出发，系统考察不同形貌纳米晶裸露晶面种类及比例、表面元素价态和分布及粒子浓度等粒子自身特性对其抗DNA氧化性能的影响，并在此基础上研究外界环境（pH、离子种类及浓度、蛋白、氨基酸及糖等）及纳米晶尺寸对不同形貌二氧化铈纳米晶抗DNA氧化性能的影响。建立纳米晶的晶面与其抗DNA氧化性能的关系，促进对二氧化铈纳米晶抗氧化机理的理解，为二氧化铈纳米晶在DNA损伤相关重大疾病防治中的应用提供理论支撑和实验依据。

二氧化铈纳米晶由于表面Ce3+/4+的存在而具有独特的抗氧化能力，使其在生物医药领域的应用引起了很大的关注。但是，目前对二氧化铈纳米晶抗氧化性能的研究存在很多矛盾的结论，这主要是由于研究所用的二氧化铈纳米晶形貌各异，并且实验条件各不相同，从而导致实验结果无法比较，也使得对纳米晶抗氧化机理认识不够，从而极大的限制了其临床应用的进展。针对这种情况，本课题从裸露不同晶面的二氧化铈纳米晶可控制备出发，考察了不同形貌纳米晶裸露晶面种类及比例对其抗DNA氧化性能的影响，并在此基础上研究了外界环境对二氧化铈纳米晶抗氧化性能的影响。. 主要研究成果如下：. 裸露不同晶面种类及比例的三种二氧化铈纳米晶对抗DNA氧化损伤性能的影响，二氧化铈纳米晶裸露晶面对抗DNA氧化损伤的能力大小依次为{100} > {110} > {111}，为二氧化铈纳米晶用于抗DNA氧化损伤保护提供了基础。. 外部•OH浓度和二氧化铈纳米晶本身浓度，材料尺寸等因素都可以引起形貌二氧化铈纳米晶氧化还原性能的反转，有助于对目前关于二氧化铈纳米晶性能研究存在的矛盾结果的理解，进一步的指出二氧化铈纳米晶表面的Ce3+的含量是决定二氧化铈纳米晶氧化还原性能的决定性因素，有利的促进了二氧化铈纳米晶临床应用的进程。. 外部环境中的离子种类能二氧化铈纳米晶抗氧化性能的影响， PO43- 和HCO3-能够与纳米粒子表面的Ce3+作用形成铈盐，阻断粒子表面Ce3+/Ce4+之间的可逆循环，导致其抗DNA氧化性能丧失，为二氧化铈纳米晶生物进一步临床应用提供了有利的参考。. 壳聚糖包覆不仅不影响二氧化铈纳米晶的抗氧化性能，还赋予其良好的水溶性和对pH的稳定性，材料可以在长达7个月后还具有良好的抗氧化性能。扩展了二氧化铈纳米晶的使用范围。. 研究了抗坏血酸对二氧化铈纳米晶抗氧化性能的影响，CeO2表面Ce3+含量随着抗坏血酸浓度的增加明显升高，抗氧化作用减弱，逐渐转化为氧化作用。建立了二氧化铈纳米晶性能的调控的方法。