“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

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.