LAUSR

Acute liver failure (ALF) is a severe liver disease caused by many reasons. One of them is the overdosed acetaminophen (APAP), which is metabolized into N-acetyl-p-benzoquinone imine (NAPQI), an excessive toxic metabolite, by CYP2E1, resulting in excessive reactive oxygen species (ROS), exhausted glutathione (GSH), and thereafter hepatocyte necrosis. N-acetylcysteine is the FDA-approved drug for detoxification of APAP, but it has limited clinical application due to the short therapeutic time window and concentration-related adverse effects. In this study, we developed a carrier-free and bilirubin dotted nanoparticle (B/BG@N), which was formed using bilirubin (an endogenous metabolite of the body) and 18β-Glycyrrhetinic acid (a metabolic component of glycyrrhiza acid in vivo), and bovine serum albumin (BSA) was then adsorbed to mimic the in vivo behavior of the conjugated bilirubin for hitchhiking. In addition, BSA modification could also improve the stability and biocompatibility of the formed nanoparticles. Our results demonstrate that B/BG@N could effectively reduce the production of NAPQI and ROS. Moreover, B/BG@N nanoparticles exhibited antioxidant effects against intracellular oxidative stress via regulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signal axis, decreasing ROS, and reducing the production of inflammatory factors. In vivo study showed that B/BG@N can effectively improve the clinical symptom of the mice model by histological and blood biochemical tests. Our study suggested that B/BG@N own increased circulation half-life, improved accumulation in the liver, and dual detoxification, providing a promising strategy for clinical ALF treatment. This article is protected by copyright. All rights reserved.