De Novo Design of Near-Infrared Fluorescent Agents Activated by Peroxynitrite And Glutathione-Responsive Imaging for Diabetic Liver Disease.

Diabetes and its complications, such as diabetes liver disease, have become 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) have been 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, we prepared two activatable agents NTCF-ONOO - and NTCF-GSH 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 was observed. Importantly, we visualized the ONOO - and GSH level in the diabetes liver disease cellular model and explored the possible redox imbalance mechanism related to NAD + and NADH in this process. Moreover, these probes can sensitively recognize ONOO - and GSH in the process of oxidative stress resulting from by 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. This article is protected by copyright. All rights reserved.