Macrophages are central to the pathogenesis of metabolic dysfunction-associated steatohepatitis (MASH), a condition driven by persistent inflammation and elevated reactive oxygen species (ROS). Nanotherapeutic strategies that simultaneously suppress inflammation and eliminate ROS thus hold significant promise. Here, we engineered mannose-modified trimethyl chitosan-coated Ti₃C₂ MXene nanozymes (MMCT) for selective targeting of hepatic macrophages via mannose receptor-mediated endocytosis. The system was designed to reduce intracellular ROS and attenuate MASH progression. MMCT effectively scavenged ROS, enhanced superoxide dismutase (SOD) activity, and inhibited the TLR4/NF-κB signaling pathway. By specifically targeting macrophages, MMCT amplified antioxidant efficacy and enabled precise localization to hepatic lesions. These effects collectively promoted repolarization of pro-inflammatory M1 macrophages toward an anti-inflammatory M2 phenotype, as indicated by downregulation of pro-inflammatory mediators. This phenotypic shift further suppressed lipid droplet accumulation. In a murine MASH model, MMCT treatment mitigated lobular inflammation and macrovesicular steatosis, restoring normal liver function. This work not only presents a novel nano therapeutic strategy for MASH but also underscores the therapeutic potential of Ti₃C₂-based nanoplatforms.
He et al. (Sun,) studied this question.