Mitochondria-Targeted Albumin Near-Infrared Fluorescent Probe for Drug-Induced Liver Injury

Human serum albumin (HSA), the most abundant plasma protein synthesized by hepatocytes, is vital for maintaining plasma colloid osmotic pressure, regulating redox balance, and transporting nutrients and metabolic wastes. Abnormal HSA levels correlate strongly with multiple diseases, especially liver disorders including cirrhosis, hepatocellular carcinoma and drug-induced liver injury (DILI), making HSA an essential biomarker for clinical diagnosis and prognosis. Although small-molecule fluorescent probes have been developed for HSA detection, major drawbacks persist: most work in the visible spectrum with poor tissue penetration, show low selectivity in complex biological environments, cannot realize subcellular localization or real-time in vivo monitoring. Herein, we fabricated a new near-infrared fluorescent probe TH from rhodamine derivatives for HSA detection. Relying on the twisted intramolecular charge transfer (TICT) mechanism, TH is weakly fluorescent in free form. When bound to the hydrophobic cavity of HSA, its molecular torsion is inhibited, producing prominent near-infrared fluorescence at 720 nm. TH possesses outstanding selectivity toward HSA, with a low detection limit of 2.3 μg/mL and favorable linear response. It also targets mitochondria, allowing real-time subcellular imaging of HSA in live cells. Further verified in a DILI mouse model, TH enables noninvasive real-time monitoring of hepatic HSA dynamics. This work offers a novel near-infrared probe for HSA analysis, holding great promise for auxiliary diagnosis and therapeutic assessment of DILI and other HSA-associated liver diseases.