Ultrasound-activated dual-nanozyme platform for targeted ROS scavenging and NO delivery in liver fibrosis therapy

Liver fibrosis (LF) is a leading cause of liver-related mortality worldwide. Although antifibrotic drugs are commonly used in clinical practice, their efficacy remains limited. Excessive reactive oxygen species (ROS) in the fibrotic liver microenvironment play a crucial role in LF progression. Nanozymes, owing to their enzyme-mimicking catalytic activity and antioxidant properties, offer a promising strategy for LF treatment. Vanadium-based nanozymes exhibit ROS-scavenging capabilities and promote fibrosis reversal, while zirconium (Zr)-based metal–organic frameworks (MOFs), such as UiO-66, possess excellent biocompatibility and catalytic activity. However, the therapeutic efficacy of nanozymes is hindered by their intrinsic catalytic limitations. Ultrasound (US), a non-invasive therapeutic modality, has been shown to enhance nanozyme activity and improve treatment outcomes. In this study, we developed a dual-nanozyme composite (UiO-66/V2C/L-Arg/pPB, UVLp) with targeted ROS-scavenging and L-arginine (L-Arg) delivery capabilities. Upon ultrasound exposure, UVLp releases L-Arg and nanozymes, facilitating nitric oxide (NO) generation, alleviating oxidative stress, and mitigating liver fibrosis. This work introduces a novel ultrasound-activated nanozyme platform for LF therapy, providing valuable insights for clinical translation.