A Biomimetic Nanoparticle Exerting Protection against Acute Liver Failure by Suppressing CYP2E1 Activity and...

Area of Science:

• Biomedical Engineering
• Nanomedicine
• Hepatology

Background:

• Acute liver failure (ALF) is a critical condition often caused by acetaminophen (APAP) overdose.
• APAP overdose leads to toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI) production, oxidative stress, and hepatocyte necrosis.
• Current treatments like N-acetylcysteine have limitations including a narrow therapeutic window and adverse effects.

Purpose of the Study:

• To develop a novel carrier-free nanoparticle (B/BG@N) for enhanced acetaminophen overdose treatment.
• To investigate the dual detoxification and antioxidant capabilities of B/BG@N.
• To evaluate the in vivo efficacy of B/BG@N in an acute liver failure mouse model.

Main Methods:

• Fabrication of bilirubin and 18β-Glycyrrhetinic acid-based nanoparticles (B/BG@N) with adsorbed bovine serum albumin.
• Assessment of NAPQI reduction and antioxidant effects via the Nrf2/HO-1 pathway.
• Evaluation of inflammatory factor production and in vivo therapeutic effects in an ALF mouse model.

Main Results:

• B/BG@N effectively reduced NAPQI production and intracellular oxidative stress.
• Nanoparticles modulated the Nrf2/HO-1 signaling pathway and decreased inflammatory factors.
• In vivo studies demonstrated improved clinical symptoms in ALF mice treated with B/BG@N.
• B/BG@N exhibited increased circulation half-life and enhanced liver accumulation.

Conclusions:

• B/BG@N demonstrates dual detoxification and antioxidant properties for acetaminophen-induced acute liver failure.
• The nanoparticle strategy shows potential for improved clinical outcomes in ALF treatment.
• B/BG@N offers a promising alternative to current therapies with enhanced pharmacokinetic properties.