A Core‐Brush Nanoplatform with Enhanced Lubrication and Anti‐Inflammatory Properties for Osteoarthritis Treatment

Abstract Osteoarthritis (OA) is recognized as a highly friction‐related joint disease primarily associated with increased joint friction and inflammation due to pro‐inflammatory M1‐type macrophage infiltration in the articular cavity. Therefore, strategies to simultaneously increase lubrication and relieve inflammation to remodel the damaged articular microenvironment are of great significance for enhancing its treatment. Herein, a multifunctional core‐brush nanoplatform composed of a ROS‐scavenging polydopamine‐coated SiO 2 core and lubrication‐enhancing zwitterionic poly(2‐methacryloyloxyethyl phosphorylcholine) (PMPC) brush and loaded with the anti‐inflammatory drug curcumin by a reactive oxygen species (ROS)‐liable conjugation (named as SiO 2 @PP‐Cur) is rationally designed. Benefiting from the grafted zwitterionic PMPC brush, a tenacious hydration layer with enhanced lubricity for reducing joint abrasions is developed. More importantly, based on the mono‐iodoacetic acid‐induced arthritis (MIA) rat model, intra‐articular injection of SiO 2 @PP‐Cur nanoplatform can effectively alleviate articular inflammation via promoting macrophage polarization from the pro‐inflammatory M1 to anti‐inflammatory M2 state by activating the nuclear factor erythroid 2‐related factor 2 (Nrf2) signaling pathway and attenuating the degradation of cartilage matrix, resulting in the remodeling of the damaged microenvironment into a pro‐regenerative microenvironment. As a result, SiO 2 @PP‐Cur can considerably inhibit OA progression. Therefore, the work may provide a novel strategy for the development of an advanced core‐brush nanoplatform for enhanced OA therapy.