Functionalized Biomimetic Nanoparticles Targeting the IL‐10/IL‐10Rα/Glycolytic Axis in Synovial Macrophages Alleviate Cartilage Degeneration in Osteoarthritis

Abstract Osteoarthritis (OA) is a low‐grade inflammatory disease that is highly associated with severe hyperplasia of the synovial membrane and the degeneration of cartilage. Interleukin‐10 (IL‐10), has been extensively studied, while its receptor, IL‐10Rα, has not been widely mentioned in the context of OA. A significant difference is found in the expression of IL‐10Rα in synovial macrophages from normal and OA patients, along with a marked increase in the glycolytic activity of synovial macrophages. In IL‐10Rα Lysm OA mice, the specific deficiency of IL‐10Rα exacerbated the progression of OA. Mechanistically, hypoxia‐inducible factor‐1α (HIF‐1α) is identified as a key transcription factor, and its inhibition significantly weakened the glycolytic process. Additionally, differences in ferroptosis of chondrocytes are observed. After co‐culturing the two types of cells in vitro, a significant connection is found between the glycolytic state of synovial macrophages and the ferroptosis of chondrocytes. To achieve targeted therapy, MI@UN, a biomimetic nanoparticle encapsulating NO‐prednisolone in UIO‐66‐NH 2 , surface‐modified with IL‐10, and coated with macrophage membranes (MM), is developed. It significantly slows osteoarthritis progression in mice. This offers new insights into OA pathogenesis, highlighting IL‐10Rα as a therapeutic target and supporting MI@UN's translational use for OA treatment.