De Novo Design of Near‐Infrared Fluorescent Agents Activated by Peroxynitrite and Glutathione‐Responsive Imaging for Diabetic Liver Disease

Abstract

AbstractDiabetes and its complications, such as diabetes liver disease, is a major problem puzzling people's health. The detection of redox states in its pathological process can effectively help us gain a deeper understanding of the disease. The pair of oxidation–reduction substances peroxynitrite (ONOO−) and glutathione (GSH) is considered to be closely related to their occurrence and development. Thus, direct visualization of ONOO− and GSH in diabetes liver disease is critical to evaluate the disease at the molecular level. Herein, two activatable agents NTCF‐ONOO− and NTCF‐GSH are prepared for selectively detecting ONOO− and GSH through protection and deprotection strategies based on hydroxyl and amino groups of near‐infrared fluorophore. Fluorescence imaging of exogenous and endogenous ONOO− and GSH changes in living cells and in vivo is observed. The ONOO− and GSH level in the diabetes liver disease cellular model are visualized and the possible redox imbalance mechanism related to the oxidized (NAD+) and reduced (NADH) nicotinamide adenine dinucleotides is explored in this process. Moreover, these probes can sensitively recognize ONOO− and GSH in the process of oxidative stress resulting from streptozotocin and streptozotocin/acetaminophen‐induced complex diabetic liver disease in vivo. In addition, they can be applied for monitoring the clinical serum sample related with diabetic patients.