Macrophage polarization determines the production of
cytokines that fuel the initiation and evolution of
rheumatoid arthritis (RA). Thus, modulation of macrophage polarization might represent a potential therapeutic strategy for RA. However, coordinated modulation of macrophages in the synovium and synovial fluid has not been achieved thus far. Herein, we develop a biomimetic
ApoA-I mimetic
peptide-modified neutrophil membrane-wrapped
F127 polymer (R4F-NM@
F127) for targeted
drug delivery during RA treatment. Due to the high expression of adhesion molecules and
chemokine receptors on neutrophils, the neutrophil membrane coating can endow the nanocarrier with
synovitis-targeting ability, with subsequent recruitment to the synovial fluid under the chemotactic effects of
IL-8. Moreover, R4F
peptide modification further endows the nanocarrier with the ability to target the SR-B1 receptor, which is highly expressed on macrophages in the synovium and synovial fluid. Long-term in vivo imaging shows that R4F-NM@
F127 preferentially accumulates in inflamed joints and is engulfed by macrophages. After loading of the anti-inflammatory
drug celastrol (Cel), R4F-NM@
F127-Cel shows a significant reduction in hepatotoxicity, and effectively inhibits synovial
inflammation and alleviates joint damage by reprogramming macrophage polarization. Thus, our results highlight the potential of the coordinated targeted modulation of macrophages as a promising therapeutic option for the treatment of RA.