Targeted platelet with hydrogen peroxide responsive behavior for non-alcoholic steatohepatitis detection

Area of Science:

• Biomedical Engineering
• Hepatology
• Medical Imaging

Background:

• Non-alcoholic fatty liver disease (NAFLD) encompasses liver abnormalities, progressing to non-alcoholic steatohepatitis (NASH) with inflammation and fibrosis.
• Timely NASH diagnosis is crucial to prevent disease progression.
• Platelets (PLTs) are implicated in NASH pathogenesis, migrating to inflamed liver sites with oxidative stress.

Purpose of the Study:

• To develop a novel diagnostic tool for non-alcoholic steatohepatitis (NASH).
• To engineer platelets for targeted delivery of a fluorescent probe to inflamed liver tissue.
• To enable sensitive and selective fluorescence imaging of NASH.

Main Methods:

• Purification of platelets (PLTs) from fresh blood.
• Engineering PLTs with a hydrogen peroxide (H2O2)-responsive fluorescent probe (5-DP) via lipid fusion, creating PLT-DPs.
• Assessing PLT-DP recruitment and fluorescence enhancement in NASH liver models.

Main Results:

• Engineered PLT-DPs were successfully recruited and trapped in NASH liver inflammation foci.
• PLT-DPs interacted with extracellular matrix components like hyaluronan and Kupffer cells.
• The fluorescence of 5-DP on PLT-DPs significantly increased in response to elevated H2O2 levels in NASH livers.

Conclusions:

• Engineered PLT-DPs demonstrate high selectivity and sensitivity for NASH fluorescence imaging.
• This approach shows significant promise for early and accurate diagnosis of NASH.
• PLT-DPs offer a potential new avenue for non-alcoholic steatohepatitis diagnostics.