Wu Qian, Hu Ziwei, Zhang Guoyang, Jin Yulong, Wang Zhuo
State Key Laboratory of Chemical Resource Engineering, College of Chemistry, Beijing University of Chemical Technology, Beijing 100029, China.
Biosensors (Basel). 2024 Dec 22;14(12):638. doi: 10.3390/bios14120638.
Peroxynitrite (ONOO) plays an important role in many physiological and pathological processes. Excessive ONOO in cells leads to oxidative stress and inflammation. However, precise monitoring of ONOO levels in specific organelles (e.g., mitochondria) is still lacking and urgently needed. Herein, we rationally designed a mitochondria-targeted ratiometric fluorescent probe, MOBDP-I, for imaging of ONOO in the mitochondria of inflammatory cells and model mice. This probe, MOBDP-I, was synthesized by conjugating a BODIPY fluorophore to a mitochondria-targeting moiety-indole-salt group by a carbon-carbon double bond (C=C). In the presence of ONOO, the C=C bond between the BODIPY backbone and the indole-salt group was oxidized and broken, leading to an 18-fold enhancement of fluorescence at 510 nm, along with a significant fluorescence decrease at 596 nm. The ratiometric response property bestowed the probe with advantages in the precise quantification of ONOO in cells, thus allowing estimation of the extent of inflammation in living cells and mouse models of rheumatoid arthritis, peritonitis, and brain inflammation. MOBDP-I could act as an effective molecular tool to study the relationship between ONOO and the occurrence and development of inflammatory diseases.
过氧亚硝酸盐（ONOO）在许多生理和病理过程中发挥着重要作用。细胞内过量的ONOO会导致氧化应激和炎症。然而，目前仍缺乏对特定细胞器（如线粒体）中ONOO水平的精确监测，这一需求十分迫切。在此，我们合理设计了一种线粒体靶向的比率荧光探针MOBDP-I，用于对炎症细胞和模型小鼠线粒体中的ONOO进行成像。该探针MOBDP-I是通过碳-碳双键（C=C）将硼二吡咯荧光团与线粒体靶向部分吲哚盐基团偶联而成。在ONOO存在的情况下，硼二吡咯骨架与吲哚盐基团之间的C=C键被氧化断裂，导致510 nm处荧光增强18倍，同时596 nm处荧光显著降低。这种比率响应特性赋予了该探针在精确量化细胞内ONOO方面的优势，从而能够评估类风湿性关节炎、腹膜炎和脑部炎症的活细胞及小鼠模型中的炎症程度。MOBDP-I可作为一种有效的分子工具，用于研究ONOO与炎症性疾病发生发展之间的关系。
