Fan Lixue, Pan Yanping, Li Weiqing, Xu Yue, Duan Yishan, Li Ruixi, Lv Yanqing, Chen Haiyan, Yuan Zhenwei
Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, 24 Tongjia Lane, Gulou District, Nanjing, 210009, China.
Department of Breast Surgery, General Hospital of Pingmei Shenma Medical Group, Pingdingshan, 467000, Henan, PR China.
Anal Chim Acta. 2021 Mar 8;1149:338203. doi: 10.1016/j.aca.2021.338203. Epub 2021 Jan 8.
Mitochondria are cellular energy factory, having an essential role in cellular metabolism. Furthermore, abnormal changes in mitochondrial viscosity have been confirmed to be closely related to many diseases. Therefore, the development of probe that responsive to mitochondrial viscosity and its application in mitochondrial viscosity measurement is considered to be a new tool for understanding diseases. In this paper, a mitochondrial viscosity probe (DICB) with a large Stokes shift (214-253 nm) was designed and synthesized by modifying the structure of the carbazole fluorophore. The probe DICB has a favorable responsive to viscosity in the near-infrared (NIR) region (703 nm). In the water-glycerol system (0.893 cP -945 cP), the fluorescence intensity of DICB at 703 nm has a 74 times increase; in the range of 5.041 cP-856.0 cp, it has a well linear fitting relationship. Meantime, the probe has excellent sensitivity to viscosity. The probe (DICB) has been confirmed to be able to detect changes of mitochondrial viscosity in cell models induced by nystatin, carbonyl cyanide m-chlorophenyl hydrazone (CCCP) and lipopolysaccharide (LPS); it has also been validated that DICB can be used in the process of autophagy to monitor mitochondrial viscosity. More importantly, DICB can be applied to the detection of abnormal mitochondrial viscosity in inflammatory tissues at the biological level. The outstanding characteristics of DICB for mitochondrial viscosity detection are not only of great importance to the development of viscosity probes, but also provides a universal strategy to study the relationship between inflammatory and mitochondrial viscosity.
线粒体是细胞的能量工厂,在细胞代谢中起着至关重要的作用。此外,线粒体黏度的异常变化已被证实与许多疾病密切相关。因此,开发对线粒体黏度有响应的探针并将其应用于线粒体黏度测量被认为是理解疾病的一种新工具。本文通过修饰咔唑荧光团的结构,设计并合成了一种具有大斯托克斯位移(214 - 253 nm)的线粒体黏度探针(DICB)。探针DICB在近红外(NIR)区域(703 nm)对黏度具有良好的响应。在水 - 甘油体系(0.893 cP - 945 cP)中,DICB在703 nm处的荧光强度增加了74倍;在5.041 cP - 856.0 cp范围内,具有良好的线性拟合关系。同时,该探针对黏度具有出色的灵敏度。已证实探针(DICB)能够检测制霉菌素、羰基氰化物间氯苯腙(CCCP)和脂多糖(LPS)诱导的细胞模型中线粒体黏度的变化;还验证了DICB可用于自噬过程中线粒体黏度的监测。更重要的是,DICB可应用于生物水平上炎症组织中线粒体异常黏度的检测。DICB用于线粒体黏度检测的突出特性不仅对黏度探针的开发具有重要意义,还为研究炎症与线粒体黏度之间的关系提供了一种通用策略。