Macrophage Polarization as a Facile Strategy to Enhance Efficacy of Macrophage Membrane‐Coated Nanoparticles in Osteoarthritis

Osteoarthritis (OA) is a chronic degenerative joint disorder associated with pain and inflammation, and is the leading cause of disability worldwide. Owing to the complexity of OA inflammation driven by a plethora of inflammatory cytokines, current specific anti‐cytokine therapies have not been successful. Among the immune cells implicated in OA inflammation, macrophages reportedly regulate OA inflammation via macrophage polarization. Given that pro‐inflammatory M1 and anti‐inflammatory M2 macrophages have opposing roles in OA inflammation, exploiting advanced polarization of macrophages to specific macrophage subsets (M0, M1, and M2) to enhance the therapeutic efficacy of macrophage membrane‐coated gold (Au) nanoparticles (NPs) as a broad‐spectrum anti‐inflammatory agent for OA treatment is proposed. Herein, it is shown that among the macrophage membrane‐coated NPs generated from the various macrophage subsets, M2 macrophage membrane‐coated nanoparticles (Au‐M2 NPs) uniquely exhibit superior efficacy in sponging the pro‐inflammatory cytokines and alleviating OA inflammation and matrix degradation over its counterparts derived from the same macrophage cell source, in both inflammation‐stimulated chondrocyte and explant OA models. Collectively, the herein described results validate macrophage polarization as a facile strategy to enhance the therapeutic efficacy of macrophage membrane NP‐based immunotherapy for potential OA treatment.