AIE-ACQ荧光团联用构建线粒体膜电位的双色型荧光探针及其生物应用

线粒体膜电位在合成ATP、细胞癌变和细胞凋亡等过程中起关键作用。目前双色、比率检测线粒体膜电位的荧光探针的设计缺乏普适性的策略。在本项目中，利用线粒体膜电位的高低可导致探针分子在线粒体上富集浓度具有显著差异的特点，申请人首次提出以非共轭形式连接具有不同荧光发射波段的聚集诱导发光(AIE)荧光团、聚集诱导荧光淬灭(ACQ)荧光团、和线粒体靶向基团构建探针的策略，开发能够双色检测线粒体膜电位的荧光探针。.新构建的探针在线粒体膜电位高时，以高浓度聚集到线粒体上，可检测到以AIE荧光团的荧光为主体的荧光信号；当线粒体膜电位低时，线粒体上探针浓度较低，可检测到以ACQ荧光团的荧光为主体的荧光信号。本项目将利用上述荧光探针系统地研究不同种类癌细胞和正常细胞线粒体膜电位的差异以及细胞在不同生理状态尤其是凋亡状态下的线粒体膜电位变化。为研究线粒体在细胞癌变以及细胞凋亡等过程中的作用机制提供理论和实验基础。

Mitochondrial membrane potential plays a key role in the process of ATP synthesis, cell carcinogenesis and cell apoptosis. At present, the design of dual-color ratiometric fluorescent probes for detecting mitochondrial membrane potential lacks a universal strategy. As the level of mitochondrial membrane potential can cause significant differences in the concentration of probe molecules in mitochondria, in this project, the applicant firstly proposes a strategy that non-conjugated combination of aggregation-induced emission (AIE) fluorophores and aggregation-caused quenching (ACQ) fluorophores with different emission, and mitochondrial targeting groups to construct probes. Using this strategy, the fluorescent probe capable of detecting mitochondrial membrane potential in dual colors can be widely developed..When mitochondrial membrane potential is in high level, the newly constructed probe molecules accumulate on mitochondria at a high concentration. So the fluorescence signal detected is mainly from AIE fluorophores. When mitochondrial membrane potential is low, the concentration of probe molecules on mitochondria is also low. So the fluorescence signal detected is mainly from ACQ fluorophores. In this project, we will systematically study the difference of mitochondrial membrane potential between different types of cancer cells and normal cells, and study the change of mitochondrial membrane potential of cells in different physiological stages, especially in apoptosis stage. This project will provide theoretical and experimental basis for the mechanism research of mitochondria in the process of cell carcinogenesis and cell apoptosis.