Fig. 1.

Schematic illustration of nanoenzyme functionalized neutrophil-derived exosomes (uPB-Exo) mediated restoring inflammation environment for effective treatment of advanced rheumatoid arthritis. (A) uPB-Exo were developed by surface engineered neutrophil-derived exosomes (NEs-Exo) with sub-5 nm ultrasmall PBNPs (uPB) via click chemistry. (B) uPB-Exo can selectively accumulate in inflamed joints, and inhibiting the production of pro-inflammatory factors and alleviating inflammatory stress in activated fibroblast-like synoviocytes (FLS), macrophages and chondrocytes. In addition, uPB-Exo effectively targeted inflammation synovitis, penetrated deeply into the cartilage and real-time visualized inflamed joint in CIA mice in vivo, leading to diagnosis of RA with high sensitivity and specificity. Particularly, uPB-Exo showed significant therapeutic efficacy in RA by ameliorating joint damage and suppressing overall arthritis severity via inducing a cascade of anti-inflammatory events via Th17/Treg cell balance regulation.