Fig. 1. Schematic illustration of DS-EXOs as a cell-free therapeutic system for RA.

(A) The surface engineering process of MSC-EXOs by the MGE-mediated click chemistry of ADSCs. This methodology facilitated the introduction of a targeting moiety onto the MSC-EXOs without causing their dysfunction. (B) Mechanism by which the DS-EXOs reprogram macrophages. After systemic administration, the DS-EXOs reach joints inflamed by RA owing to their ability to target activated macrophages. Macrophage reprogramming in RA can be effectively promoted by the targeted delivery of the DS-EXOs. MVB, multivesicular bodies.