A water-soluble H2O2-activatable NIR fluorescence/photoacoustic probe with viscosity-modulated output for longitudinal imaging of drug-induced liver injury

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Drug-induced liver injury (DILI) involves oxidative stress and remodeling of the hepatocellular microenvironment. Here, we designed and evaluated two structurally related near-infrared probes, TNO-1 and TNO-2 . TNO-1 exhibited an aqueous solubility of 0.71 mg mL⁻¹ and responded to H 2 O 2 with a detection limit of 0.094 μM. H 2 O 2 -dependent oxidation generated the phenolic product OH-TNO-1 , producing enhanced long-wavelength fluorescence and photoacoustic signals. OH-TNO-1 retained viscosity-sensitive fluorescence consistent with restriction of intramolecular motion. In cultured cells and APAP-challenged mice, TNO-1 produced increased imaging signals that were attenuated by NAC treatment. Comparative experiments using OH-TNO-1 supported a sequential response model in which H 2 O 2 -dependent activation is followed by viscosity-sensitive modulation of the optical output. These findings establish TNO-1 as a proof-of-concept FL/PA platform for longitudinal imaging of APAP-induced liver injury and therapeutic response. Validation in larger animal cohorts, additional liver-injury models, and quantitative correlation with established injury biomarkers will be required to define its diagnostic performance.

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