Janus Graphene Oxide Nanoplatform with Oppositely Functionalized Adhesion and Lubrication Enables Local Sustained Fenofibrate Release to Synergistically Halt Osteoarthritis

Abstract Osteoarthritis (OA) progresses via a destructive cycle involving cartilage damage, friction, lubrication loss, and chondrocyte senescence. Current therapies, limited to temporary lubrication or pain relief, fail to halt OA due to their inability to repair cartilage or restore innate lubrication. To address this challenge, an asymmetric Janus graphene oxide (MGO) nanoplatform is engineered and functionalized with the anti‐senescence agent Fenofibrate (FN), creating the MGO‐FN system. This integrated design features one side providing robust cartilage adhesion and the opposing side offering superior lubrication, while simultaneously delivering the therapeutic FN. Critically, the nanoscale MGO‐FN effectively infiltrates and fills micro‐damage on the cartilage surface, enabling localized and sustained FN release. This maximizes drug bioavailability at the target site by minimizing diffusion distances. In vitro, MGO‐FN demonstrated potent synergistic effects, significantly enhancing chondrocyte proliferation and extracellular matrix synthesis, reducing senescence, and upregulating the lubrication marker PRG4 more effectively than either component alone. In vivo OA rat studies, supported by transcriptomics analysis, validated MGO‐FN's potent therapeutic effects, including reduced cartilage degradation, mitigated inflammation, promoted matrix regeneration, and restored innate lubrication. These findings underscore MGO‐FN as a promising multifaceted therapeutic strategy to halt OA progression by concurrently restoring cartilage integrity and lubricating function.