Regulation of Synovial Macrophages Polarization by Mimicking Efferocytosis for Therapy of Osteoarthritis

Abstract The progression of osteoarthritis is associated with chronic synovitis caused by synovial macrophage infiltration and proinflammatory M1 polarization. Accordingly, repolarization of macrophages from the M1 to M2 phenotype by nanoagents is proposed as a potential treatment strategy. However, achieving adequate effects using intra‐articular injected agents is challenging due to the rapid drug clearance from the joint space and poor efficiency of nanoparticles endocytosis by synovial macrophage cells. Herein, apoptotic chondrocyte membrane‐coated, quercetin‐loaded metal‐organic framework nanoparticles as immunomodulators for treating osteoarthritis are reported. The apoptotic chondrocyte membrane‐camouflaged nanoparticles containing various natural “eat me” signals can be easily disguised as chondrocyte apoptotic bodies in the joints, and thus are more easily phagocytized by synovial macrophages similarly to efferocytosis. Furthermore, the released quercetin promotes the polarization of synovial macrophages to the M2 phenotype and also inhibites the apoptosis of articular chondrocytes. In vivo results suggest that such a “Trojan horse” strategy can extend the retention time of nanoparticles in osteoarthritis joints and improve treatment efficacy. Collectively, it is hoped that this study can offer a potential and universal platform for engineered cell membrane‐coated nanoparticles to resolve inflammation by simulating specific inflammatory processes.