系列表面功能化量子点与线粒体相互作用机理研究

The biological effects of surface functionalized nanomaterials such as quantum dots (QDs), is solved one of the topics at the forefront. In this project, the multiple functionalized QDs are selected as the object of research and the mitochondria isolated from rat liver are used as biological models. The thermodynamics and dynamics properties of their interaction are investigated by using oxygen electrode, modern microcalorimetric technique, transmission electron microscopy, spectroscopic methods and biochemical analysis techniques. The influence of mitochondrial metabolism and its mechanisms, which affected by QDs with different surface modification, particle size and shell, are investigated systematically on the structure and function. The dynamic changes in mitochondrial morphology are observed by microscopic method and the changes in mitochondrial function are also analyzed microscopically. The variation rules of mitochondrial membrane permeability hole MPT, mitochondrial ion channel transport, the activity of main enzymes together with the release of cytochrome C, are investigated completely and the apoptosis factors by QDs or other nanomaterials are further explored from the perspective of mitochondrion. The mechanism of QDs biological effects are further understood and novel method of QDs biological effects are developed. These will provide quantitative data and theoretical basis for design of QDs with low-toxicity and high biocompatibility and for application of QDs in biomedical fields.

表面功能化量子点等纳米材料的生物效应是当前亟待解决的前沿课题之一。本项目以前期开发的系列表面功能化量子点为主要对象，将宏观和微观研究手段相结合，采用氧电极、微量热、透射电镜、光谱学和生化分析技术，从热动力学角度出发，在亚细胞水平上，从结构和功能上系统研究不同表面修饰、粒径大小和不同壳层包覆量子点对线粒体代谢动态过程的影响及其机制；采用显微手段观察线粒体形态结构的动态变化，从微观上解析线粒体功能变化；研究线粒体膜渗透孔MPT、线粒体离子通道转运、主要功能酶活性及细胞色素C释放的变化规律，从线粒体层面进一步探讨量子点等纳米材料诱导细胞凋亡成因；从结构和功能上，深化对量子点生物效应机制的认识，从宏观到微观建立量子点生物效应研究的新方法，为低细胞毒性、高生物相容性量子点等纳米材料的设计及其在生物医学领域的深入应用提供定量数据和提供理论依据。

表面功能化量子点等纳米材料的生物效应是当前亟待解决的前沿课题之一。本项目合成了高质量不同表面修饰（巯基丙酸、巯基乙胺、N-乙酰-L-半胱氨酸和血清白蛋白等）、不同壳层包覆及不同粒径大小的量子点，利用微量热技术深入研究各类量子点对线粒体代谢的影响，并对相应的谱图进行热动力学分析，计算其动力学参数(如代谢过程的焓变、代谢速率常数、代谢激活能等)，同时借助显微技术和生化分析技术探讨了量子点对线粒体代谢影响的内在机理，采用显微手段观察线粒体形态结构的动态变化，从微观上解析线粒体功能变化；研究了线粒体膜渗透孔MPT、线粒体离子通道转运、主要功能酶活性及细胞色素C释放的变化规律，从线粒体层面进一步探讨量子点等纳米材料诱导细胞凋亡成因，实验结果发现，量子点可以抑制线粒体呼吸酶的活性、增大线粒体内膜氢、钾离子的渗透性、导致线粒体发生渗透转换过程。这些结果可促使人们在亚细胞层面上对量子点的生物效应有更全面的认识。本项目从结构和功能上，深化对量子点生物效应机制的认识，从宏观到微观建立量子点生物效应研究的新方法，为低细胞毒性、高生物相容性量子点等纳米材料的设计及其在生物医学领域的深入应用提供定量数据和理论依据。该项目的相关研究工作共发表SCI源刊论文12篇，其中影响因子>3.0的7篇，获授权国家发明专利1项。