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

Abstract

Diabetes 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.