A multifunctional chitosan-based nanozyme (1-CS@vitexin) with enzyme-mimicking and photothermal synergistic effects for targeted liver fibrosis therapy

Abstract

Liver fibrosis, driven by excessive extracellular matrix deposition and hepatic stellate cell (HSC) activation, remains a major clinical challenge. Here, we developed a multifunctional chitosan-based nanozyme ( 1-CS@vitexin ) by integrating the natural flavonoid vitexin into a nitrogen-coordinated framework. The composite exhibits multi-enzyme-mimicking activities (oxidase-, catalase-, and peroxidase-like) that efficiently regulate reactive oxygen species (ROS) and maintain catalytic stability under acidic conditions. Moreover, 1-CS@vitexin shows strong NIR-II absorption and a high photothermal conversion efficiency (η = 52%), achieving stable light-to-heat transformation. In vitro , 1-CS@vitexin significantly inhibited TGF-β1–induced HSC activation, reduced ACTA2, TGFB1, and COL1A1 expression, and suppressed IL-6 secretion. These findings demonstrate that 1-CS@vitexin synergistically modulates oxidative stress, fibrosis, and inflammation, offering a promising catalytic–photothermal platform for effective liver fibrosis therapy.