A multifunctional L-arginine-linked melanin Nanozyme for Theranostic applications in liver fibrosis: Non-invasive dual-modal imaging and reactive oxygen species scavenging for Pyroptosis suppression.

Liver fibrosis, a pivotal pathological stage in the progression of chronic liver diseases to cirrhosis and hepatocellular carcinoma is characterized by liver sinusoidal endothelial cell (LSEC) capillarization, oxidative stress imbalance, and cell pyroptosis. Current clinical interventions show limited efficacy in reversing fibrosis, highlighting the urgent need for novel therapeutic strategies. In this study, we developed an L-arginine-loaded melanin-like nanozyme (L-Arg@MeNPs) that targets liver fibrosis through a triple-action mechanism: (1) sustained nitric oxiderelease from L-Arg restores LSEC fenestration, improving sinusoidal permeability; (2) the MeNPs exhibit catalase/superoxide dismutase-mimicking activity to scavenge reactive oxygen species, thereby blocking the NOD-like receptor pyrin domain-containing 3/caspase-1-mediated pyroptosis pathway; and (3) intrinsic photoacoustic/magnetic resonance dual-modal imaging enables real-time therapeutic monitoring. Overcoming the biosafety limitations of conventional metal-based nanozymes, this system demonstrates superior pH stability and metabolic degradability. In vivo studies confirm that L-Arg@MeNPs effectively ameliorate the fibrotic microenvironment and reduce excessive extracellular matrixdeposition, offering a targeted, safe, and theranostic solution for clinical liver fibrosis treatment.