Confined Cascade Metabolic Reprogramming Nanoreactor for Targeted Alcohol Detoxification and Alcoholic Liver Injury...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Hepatology

Background:

• Alcoholic liver injury (ALI) is a major cause of liver disease with limited treatment options.
• Current therapies for ALI are primarily supportive and do not directly metabolize alcohol.

Purpose of the Study:

• To develop a metabolic reprogramming strategy for targeted alcohol detoxification and ALI management.
• To engineer a confined cascade nanoreactor for efficient alcohol metabolism.

Main Methods:

• Designed a nanoreactor (AA@mMOF) by assembling alcohol oxidase (AOx) and aldehyde dehydrogenase (ALDH) enzymes within a mesoporous metal organic framework (mMOF) nanozyme.
• Utilized confined AOx/CAT/ALDH cascade reactions for alcohol degradation and detoxification.
• Evaluated the nanoreactor's efficacy in alcohol-intoxicated and chronically alcoholic mouse models.

Main Results:

• AA@mMOF demonstrated high-efficiency alcohol degradation (>0.5 mg·mL⁻¹·h⁻¹) with minimal aldehyde accumulation.
• In vivo studies showed significant reduction in blood alcohol concentration and rapid reversal of acute liver injury.
• The nanoreactor alleviated liver fat accumulation and oxidative stress in chronic alcoholism models, blocking ALI progression.

Conclusions:

• The confined cascade nanoreactor (AA@mMOF) offers a powerful strategy for targeted alcohol detoxification and ALI management.
• This metabolic reprogramming approach represents a paradigm shift for treating alcohol-related metabolic diseases.
• AA@mMOF shows promise for blocking and reversing the progression of alcoholic liver injury.