Pd@CeO ₂ core-shell heteronanostructures with enhanced multienzyme activity for macrophage polarization and in flammation alleviation

The high expression of classically activated macrophages (M1) subtypes and the elevated levels of reactive oxygen species (ROS) are specifically observed in osteoarthritis (OA) patients. In this study, we synthesized a Pd@CeO₂ nanozyme with a core-shell hetero-nanostructure that enhances enzyme activity through shell-core electron transfer. The goal of this work was to look into the potential of Pd@CeO₂ nanozyme in scavenging ROS and regulating macrophages for the treatment of OA. The results demonstrated that the Pd@CeO₂ nanozyme displayed multiple enzyme-like antioxidative activities, efficiently eliminating excessive intracellular ROS. This resulted in a significant decrease in the release of pro-inflammatory cytokines, consequently leading to a decline in the presence of M1-type macrophages. Furthermore, the Pd@CeO₂ nanozyme showed excellent potential in promoting the shift of macrophages toward the M2 phenotype. Additionally, the factors secreted from the cell supernatant of Pd@CeO₂-treated macrophages treated with Pd@CeO₂ demonstrated anti-inflammatory properties in the chondrocytes located within inflamed synovial joints. These findings offer valuable insights into the advancement of effective enzyme-mimetic therapies for the treatment of OA.