Construction of a hydrogen peroxide-responsive near-infrared fluorescent probe and the biological application in tracking inhalation lung injury

Inhalation lung injury (ILI) is an inflammation-driven disease primarily mediated by oxidative stress. Accordingly identifying oxidative stress-related factors is crucial for early diagnosis and timely intervention of ILI. Hydrogen peroxide (H₂O₂), one of the important reactive oxygen species (ROS), has been shown to be a key regulator in the onset and progression of ILI, with its levels dynamically reflecting the extent of oxidative stress. The selective detection of H₂O₂ using fluorescence imaging technology is a promising method for ILI detection. Herein, the fluorescent probe SRHFP based on a H₂O₂-triggered structural self-rebuilding procedure including successive three-step oxidation, self-immolation and covalent bond assembly has been developed for real-time H₂O₂ monitoring. SRHFP performs the advantageous optical properties, such as low detection limit of 0.1 μM under physiological conditions, NIR emission band centered at 660 nm to avoid tissue autofluorescence, large Stokes shift of 230 nm to minimize fluorescence self-quenching, and remarkable stability. Probe SRHFP has capability of sensitively monitoring both endogenous and exogenous H₂O₂ in A549 cells and accurately detecting various toxic chemical gases-induced lung injury model cells. What’s more, SRHFP possesses the characteristic of priority lung accumulation and was successfully applied to monitor the H₂O₂ elevation in the lungs of ILI model mice induced by inhalation of toxic gas and the decrease of H₂O₂ concentration in dexamethasone-treated mice, confirming the strong correlation between H₂O₂ levels and ILI pathological process. This probe enables dynamic visualization of ILI progression and holds significant potential as a diagnostic tool for inflammation-related lung diseases.