Biomimetic and inflammation-targeted nanoparticles for rheumatoid arthritis therapy via M1-macrophages apoptosis and polarization

M1 macrophages enrich in rheumatoid arthritis (RA) joints and contribute to persistent progression of inflammation and destruction. Their apoptosis and polarization toward M2 phenotype play crucial roles in anti-inflammation. Herein, we developed three kinds of biomimetic nanoparticles (NPs) derived from different cells for dual-targeting to inflamed site and M1 macrophages. These NPs were aimed to induce M1 macrophages apoptosis and re-polarization for efficient RA therapy via dually targeting drug delivery to inflamed joints and M1 macrophages. Results demonstrated that the NPs had a massive accumulation at inflamed site and high internalization efficiency in M1 macrophages. After loading methotrexate, the NPs substantially suppressed the viability of activated macrophages and the expression of pro-inflammatory cytokines. Furthermore, they dramatically promoted the expression of anti-inflammatory cytokines, and induced M1-to-M2 transition of macrophages. In an adjuvant-induced arthritis mouse model, the NPs efficiently reduced the number of inflammatory macrophages, secretion of pro-inflammatory cytokines and destruction of cartilage or bone tissues. Additionally, the swelling of paw and ankle joint was significantly alleviated by the NPs after 17 days treatment, especially the activated macrophage-derived NPs. The findings highlight the potential of NPs with dual-targeting ability in the treatment of RA by apoptosis and re-polarization of M1 macrophages.