Ta₄C₃ MXene Slows Progression of Fatty Liver Disease through Its Anti-Inflammatory and ROS-Scavenging Effects

Treating metabolic dysfunction-associated fatty liver disease (MAFLD) and reducing the occurrence of MAFLD-associated liver cancer remain challenging. Two-dimensional (2D) tantalum carbide (Ta₄C₃) MXene nanozymes (MXenzymes) exhibit antioxidant and anti-inflammatory activities and have thus attracted considerable attention in the fields of oncology and engineering. However, the potential mechanism of action and bioactive properties of Ta₄C₃ in MAFLD remain uncertain. In our study, Ta₄C₃ not only inhibited lipid accumulation and disrupted lipid metabolism in hepatocytes but also reduced cell death caused by fatty acids by decreasing intracellular reactive oxygen species (ROS) levels, which significantly promoted the polarization of M1 macrophages to M2 macrophages by alleviating oxidative stress and further suppressing inflammatory factor expression. In mice fed a methionine-choline-deficient (MCD) diet, Ta₄C₃ reduced lipid accumulation, the infiltration of inflammatory cells, and liver cell apoptosis by modulating the cellular microenvironment through its anti-inflammatory and antioxidant properties. Therefore, Ta₄C₃ can be used as a multifunctional bioactive material to alleviate hepatic steatosis and inflammation in individuals with MAFLD/metabolic dysfunction-associated steatohepatitis (MASH) because of its robust antioxidant and anti-inflammatory effects.