Visualizing Detection of Diabetic Liver Injury by a Biomarker-Activatable Probe via NIR-II Fluorescence Imaging

Diabetes characterized by hyperglycemia is a chronic metabolic disease with increasing prevalence worldwide, and over time it leads to damage to various organs including the liver. As the liver is the major organ for glucose metabolism, patients with diabetes are prone to liver injuries or damages; and without timely and effective treatment, diabetic liver injury may further deteriorate into serious or life-threatening complications including liver cancer or liver failure. Hence, the accurate detection of diabetic liver injury is of great significance for diabetic patients in terms of improving quality of life. Herein, a fluorescent probe (TTX-P) has been developed for in situ detection and imaging of diabetic liver injury in the near-infrared second-window (NIR-II) region. In routine clinical practice, alkaline phosphatase (ALP) is one of the most commonly assayed enzymes, and thus serving as an important diagnostic biomarker for liver dysfunction or injury. The probe TTX-P responds in situ to the overexpressed ALP in liver and thus giving out strong NIR-II fluorescence as the reporting signals for detection and imaging. The NIR-II probe TTX-P consists of the NIR-II chromophore TTX-OH as the fluorophore and phosphate group as the responsive unit. Without the presence of ALP, the probe TTX-P displays weak fluorescence because the electron-withdrawing phosphate group weakens the electron-pushing capability of the electron-donor side of the NIR-II fluorophore. While in the presence of ALP, the phosphate group is cleaved by the enzyme and consequently the fluorophore emits evident NIR-II fluorescence. The probe TTX-P has been applied in imaging liver injury in diabetic mice. The approach provides a utilitarian means for visualizing detection of diabetic liver injury in mice with NIR-II fluorescence imaging.