Injury-Retention Strategy for Discriminative Magnetic Resonance Imaging and Enhanced Antioxidant Therapy of Drug-Induced Liver Injury.

Abstract

Drug-induced liver injury (DILI) is a prevalent cause of acute liver failure worldwide, characterized by impaired hepatic clearance which creates an opportunity for targeted nanomedicine. We present an injury-retention strategy for DILI management using a gadolinium hexacyanoferrate nanozyme (GdHF). This nanozyme enables simultaneous high-fidelity diagnosis and sustained treatment. It intrinsically combines high longitudinal relaxivity (r₁ = 13.23 mM^-1·s^-1, 3.9-fold greater than Gd-DTPA) with multienzyme mimetic activities. In an acetaminophen-induced DILI model, GdHF specifically accumulated in injured liver tissue due to impaired clearance, generating strong MR contrast that clearly discriminated injured from healthy tissue. Concurrently, it provided sustained local therapy by scavenging reactive oxygen and nitrogen species (RONS). This dual action significantly alleviated oxidative stress, inflammation, and hepatocyte damage, demonstrating efficacy comparable or superior to <i>N</i>-acetylcysteine in delayed treatment scenarios. Our retention-based approach synchronizes precise imaging with localized antioxidant therapy, offering a promising strategy for DILI and other RONS-related pathologies.