Peroxidase modification-driven silymarin liposomes for the treatment of liver fibrosis

Liver fibrosis, characterized by excessive deposition of extracellular matrix (ECM), is a key pathological process in chronic liver disease. Persistent oxidative stress (OS), primarily caused by high levels of reactive oxygen species (ROS), can directly activate hepatic stellate cells, induce hepatocyte apoptosis and trigger inflammatory responses. We modified the surface of silymarin (SIL)-carrying liposomes with catalase (CAT) to treat liver fibrosis. CAT is an endogenous antioxidant enzyme that is primarily responsible for removing hydrogen peroxide generated by oxidative stress. SIL is a traditional liver-protective dietary supplement. In vitro experiments showed that CAT-LP exhibited low cytotoxicity towards normal hepatocytes (L-02 cells) and could be effectively taken up by hepatic stellate cells (JS1 cells), inducing apoptosis. Additionally, CAT-LP effectively alleviated TGF-β-induced oxidative stress by scavenging ROS, demonstrating more complete release in an H₂O₂-enriched environment. In vivo experiments revealed that CAT-LP treatment significantly reduced malondialdehyde (MDA) and transaminase (ALT and AST) levels, increased superoxide dismutase (T-SOD) content and reduced the secretion and deposition of type III procollagen. In summary, combining CAT and SIL effectively improved liver fibrosis in mice by inhibiting ROS-mediated effects and through the synergistic action of hepatoprotective drugs.