Ultrasound-activated dual-nanozyme platform for targeted ROS scavenging and NO delivery in liver fibrosis therapy
Xiujuan Yin, Shuqin Xue, Jiaqi Ji, Mingyu Zhao, Min Shao, Likang Yin, Saisai Zhang, Lei Liu, Бин Ли, Lei Zhang, Yuan Li, Xiao Wang
Abstract
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/V 2 C/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.