Fe2+ imaging in ferroptosis and drug-induced liver injury with a ratiometric near-infrared fluorescent probe

Recently, great attention has been given to the detection of ferrous ion (Fe2+) in live organisms because it plays a vital role in life and is associated with ferroptosis and many diseases. Near-infrared (NIR) ratiometric fluorescence probes are essential tools, however, such probes for tracking Fe2+ in iron-associated diseases in vivo are rarely reported. Herein, we report a novel NIR ratiometric fluorescent probe NRF-Fe2+ for Fe2+ based on a fluorescence resonance energy transfer (FRET) system using the N-oxide chemistry. This probe shows significant ratiometric fluorescence changes (λem shifts from 460 nm to 675 nm) for Fe2+ with high selectivity and sensitivity, and can image both exogenous and endogenous Fe2+ in cells with low cytotoxicity and ratiometric fluorescence signals. The imaging of Fe2+ in mice with NRF-Fe2+ is also successfully applied. Finally, we demonstrate that the probe can be applied for monitoring the level changes of Fe2+ in ferroptosis and drug-induced liver injury. All the results show that NRF-Fe2+ is a useful tool for the detection of biological Fe2+ and the study of iron-related diseases.