Acetaminophen (
N-acetyl-p-aminophenol,
APAP) is a common
antipyretic agent and
analgesic. An overdose of
APAP can result in acute liver injury (ALI). Oxidative stress and
inflammation are central to liver injury.
N-acetylcysteine (NAC), a precursor of
glutathione, is used commonly in clinical settings. However, the window of NAC treatment is limited, and more efficacious alternatives must be found. Endogenous
cytokines such as
fibroblast growth factor (FGF) 21 can improve mitochondrial function while decreasing intracellular oxidative stress and inflammatory responses, thereby exhibiting
antioxidant-like effects. In this study, self-assembled nanoparticles comprising
chitosan and
heparin (CH) were developed to deliver
FGF21 (CH-FGF21) to achieve the sustained release of
FGF21 and optimize the in vivo distribution of
FGF21. CH-FGF21 attenuated the oxidative damage and intracellular
inflammation caused by
APAP to hepatocytes effectively. In a murine model of
APAP-induced hepatotoxicity, CH-FGF21 could alleviate ALI progression and promote the recovery of liver function. These findings demonstrated that a simple assembly of CH nanoparticles carrying
FGF21 could be applied for the treatment of
liver diseases.