活细胞内靶向不同细胞器增强型极性荧光探针的研究

The abnormal changes of intracellular polarity are closely linked with disorders and diseases, such as hepatic cirrhosis, diabetes etc. In addition, cells consist of many types of organelles with different structures and functions. The microenvironments (such as polarity) in various organelles are different. Thus, it is significant that accurate monitoring of the polarity of a certain organelle. Although some polarity–sensitive fluorescent probes were reported, there are no probes to show specific subcellular organelle distributions. And the fluorescence intensity of the probe decreased rather than increased with the increase of the solution polarity, so it is difficult to be used for determination of the polarity of specific organelles. Herein, a series of PET-based enhanced fluorescent probes for polarity were developed. The derivatives dyes from BODIPY were modified by the appropriate electron donor and electron-acceptor group at the 8-position and 2, 6-position, respectively; and introduction of different organelle location groups enables the series of probes to selectively locate different organelles in living cells. Then the probes will be applied to measurement and imaging of the polar changes in specific organelles under different pathological conditions. Upon the completion of our project, we will obtain highly polarity-sensitive dye fluorescent probe which is organelle-targeted, offering a new excellent analytical method for the investigation of pathogenic mechanism and early diagnosis of cancer.

细胞极性异常与肝硬化、糖尿病等疾病密切相关。而细胞由多种细胞器构成，它们结构和功能各不相同，因此细胞器内的微环境如极性也是不同的，所以精确地监测特定细胞器的极性具有重要的生物学意义。但近年开发的极性探针不能进行细胞器定位，没有靶向性；随着溶液极性的增大，探针的荧光强度降低而不是增强，难以用于特定细胞器极性的测定。本项目基于PET原理，在BODIPY染料母体的8-位和2, 6-位分别修饰适当的供电子和吸电子取代基，得到荧光增强型极性探针；并且通过引入不同的细胞器定位基团，使得该系列探针能够选择性定位于不同细胞器，进而试用于不同病理条件下，活细胞内特定细胞器极性变化的检测和可视化，这将为利用荧光成像观测不同细胞器极性的变化来研究癌症的发生提供可能性，对该疾病的早期预警具有重要意义。

细胞极性异常与肝硬化、糖尿病等疾病密切相关。而细胞由多种细胞器构成，它们结构和功能各不相同，因此细胞器内的微环境如极性也是不同的，所以精确地监测特定细胞器的极性具有重要的生物学意义。基于PET原理，在BODIPY染料母体的8-位和2, 6-位分别修饰适当的供电子和吸电子取代基，得到荧光增强型极性探针；并且通过引入不同的细胞器定位基团，使得该系列探针能够选择性定位于不同细胞器，进而试用于不同病理条件下，活细胞内特定细胞器极性变化的检测和可视化。在此基础下，本项目共发表SCI论文2篇，为极性荧光探针的设计与合成提供了新思路。