线粒体靶向多功能铈纳米簇在辐射防护中的作用及其机制研究

It is a hot and difficult problem to search effective radiation protection drug, therapeutic target, and establish radiation damage targeted protection strategy on the combination of them. On the basis of existing literature reports and work, this research tries to explore mitochondrial targeted radiation damage protection new strategy based on albumen mediated synthesis ceria nanocluster. It intends to build multifunction cerium nanocluster system which has controlled enzymatic activity and mitochondria targeted feature. While the water-soluble, stability and biocompatibility of the material are solved effectively, the efficiency, selectivity and reproducibility of radical scavenging are also endowed to it. In the cellular level, the mitochondrial targeted of the cerium nanocluster system should be confirmed. Then, establish mitochondrial targeted radiation damage protection strategy on the basis of multifunction cerium nanocluster. It can effectively avoid the DNA suffering ROS mediated free radical damage. The exact damage mechanism of the above mentioned strategy should be also researched. In the animal level, the actual effect of above mentioned strategy against acute or chronic radiation injury should be verified. This research could enhance the survival quality of the patients with radiation injury, improve far late effect of radiation damage and have significant scientific meaning.

寻找高效的抗辐射药物，探索新的辐射损伤治疗靶点，并将其有机结合起来建立辐射损伤靶向防护策略是目前的一个热点和难点问题。在已有的文献报道和工作基础上，本申请项目提出了一种基于蛋白介导合成铈纳米簇的线粒体靶向辐射损伤防护新策略。拟构建一种线粒体靶向且酶学活性可控的多功能化铈纳米簇体系，在有效解决材料水溶性、稳定性及生物相容性的同时，赋予其自由基清除的高效性、选择性及可再生性；细胞水平上，确定其线粒体靶向定位作用，建立基于线粒体靶向的多功能化铈纳米簇辐射损伤防护策略，有效避免细胞核DNA受到线粒体活性氧介导的持续性间接自由基损伤，并阐明其确切辐射防护作用机制；动物水平上，进一步验证其对急慢性辐射损伤防护治疗的实际效果。此项研究工作对提高辐射损伤患者的生存质量，改善辐射损伤带来的远后期效应具有重要的科学意义。

探索新的辐射损伤治疗靶点，建立辐射损伤靶向防护策略是目前的一个热点和难点问题。本项目对蛋白介导合成铈纳米簇进行修饰，构建得到一种线粒体靶向且具有多种酶学活性的铈纳米簇体系，在有效解决材料水溶性、稳定性及生物相容性的同时，赋予其抗氧化性；细胞水平上，确定其线粒体靶向定位作用，建立基于线粒体靶向的多功能化铈纳米簇辐射损伤防护策略，有效避免细胞核DNA受到线粒体活性氧介导的持续性间接自由基损伤，并阐明其确切辐射防护作用机制；动物水平上，验证其对辐射损伤防护治疗的实际效果。另外，拓展研究其能够协同药物实现协同抗炎抗氧化效应，也为进一步的协同辐射损伤防护奠定了一定的基础。