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.