Target-Engineered\nLiposomes Decorated with Nanozymes\nAlleviate Liver Fibrosis by Remodeling the Liver Microenvironment

Liver fibrosis is a pathological repair response that\noccurs after\nsustained liver damage, and prompt intervention is necessary to prevent\nliver fibrosis from developing into a potentially life-threatening\ncondition. In long-term liver injury, damaged hepatocytes produce\nexcessive amounts of reactive oxygen species (ROS), which activate\nhepatic stellate cells (HSCs). This activation leads to excessive\naccumulation of extracellular matrix proteins in liver tissue. Additionally,\nliver macrophages contribute to the inflammatory microenvironment\nin the hepatic fibrotic process, exacerbating liver fibrosis through\nROS production and the secretion of pro-inflammatory factors. To address\nthe dysregulation of the hepatic microenvironment associated with\nliver fibrosis, we developed cerium oxide nanozymes using hyaluronic\nacid (HA) as a template and decorated them on the surface of liposomes\nloaded with oleanolic acid (OA). We named this prepared and obtained\ntarget-engineered liposome HCOL. The inherent superoxide dismutase\n(SOD) and catalase (CAT) activities of HCOL enabled it to effectively\nscavenge ROS in HSCs and alleviate the hypoxic conditions characteristic\nof fibrotic livers. Furthermore, HCOL reduced the concentrations of\nROS in macrophages, promoting a shift in macrophage polarization from\nthe pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype.\nThis transition increased the production of the anti-inflammatory\ncytokine interleukin 10 (IL-10), which contributed to the mitigation\nof the inflammatory microenvironment. Consequently, this therapeutic\napproach proves effective in decelerating the advancement of liver\nfibrosis.