“Three-key-and-lock” near-infrared fluorescent probe for dual-channel tracking ONOO− in mitochondria and viscosity in lysosomes in ferroptosis and drug-induced liver injury

• Published in: Dyes and pigments Vol. 225; p. 112102
• Main Authors: Liu, Yunfan, Wang, Xuyan, Fu, Nanyan, Wang, Guimei
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.06.2024
• Subjects: Dual-organelle targeting; Ferroptosis and drug-induced liver injury (DILI); Fluorescent probe; ONOO− in mitochondria and viscosity in lysosomes; ONOO− in mitochondria and viscosity in lysosomes; Dual-organelle targeting; Ferroptosis and drug-induced liver injury (DILI); Fluorescent probe
• ISSN: 0143-7208; 1873-3743
• DOI: 10.1016/j.dyepig.2024.112102

The processes of ferroptosis and drug-induced liver injury (DILI) correlate closely to oxidative stress in mitochondria which will affect intracellular microenvironmental parameters such as lysosomal viscosity. Therefore, it is of great significance to dynamically monitor ONOO− in mitochondria and viscosity in lysosomes for understanding redox signal transduction but remains challenging. Here we report a near-infrared fluorescent probe, HCy-OH-mito, which has the dual-organelle targeting ability for the detection of ONOO− in mitochondria and viscosity in lysosomes via a “three-key-and-lock” strategy. HCy-OH-mito has been successfully applied to independently and simultaneously label mitochondria and lysosomes in live cells, and monitor the fluctuations of ONOO− in mitochondria and viscosity in lysosomes during ferroptosis and APAP-induced liver injury and in live zebrafish. [Display omitted] •A ONOO−/pH/viscosity-activated NIR fluorescent probe HCy-OH-mito has been constructed. The sensing mechanism has been discussed.•HCy-OH-mito showed a good dual-organelle targeting ability and was successfully applied for dual-channel tracking ONOO− levels in mitochondria and viscosity in lysosomes in live cells.•By virtue of a “three-key-and-lock” strategy, variations of ONOO− levels in mitochondria and viscosity in lysosomes were in situ visualized during the cell ferroptosis.•The probe was also successfully used for the fluorescence imaging of ONOO− produced in a model of APAP-induced liver injury and in live zebrafish.