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However, most current RA treatments are single\u2010target interventions, exerting limited impact on RAM. Herein, apoptotic extracellular vesicles (ApoEV) are constructed for programmable regulation of the neutrophil\u2010macrophage\u2010ROS pathogenic axis, aiming to reconstruct RAM and improve RA therapy. Mesenchymal stem cells (MSCs) are pretreated with dexamethasone (Dex) and induced apoptosis to produce Dex\u2010loaded and FasL\u2010overexpressing ApoEV (D@ApoEV\n                    <jats:sup>FasL<\/jats:sup>\n                    ), which is further modified with low\u2010molecular\u2010weight heparin (LMWH) through a ROS\u2010responsive cleavage linker to form D@ApoEV\n                    <jats:sup>FasL<\/jats:sup>\n                    \u2229L. After intravenous injection into RA mice, D@ApoEV\n                    <jats:sup>FasL<\/jats:sup>\n                    \u2229L targeted the inflamed joints based on their MSC\u2010derived feature and blocked neutrophil recruitment through binding to P\u2010selectin on vascular endothelial cells. In response to high ROS, D@ApoEV\n                    <jats:sup>FasL<\/jats:sup>\n                    \u2229L shed LMWH and exposed FasL, inducing neutrophil apoptosis through the Fas\/FasL signaling pathway. Subsequently, the apoptotic neutrophils triggered macrophage reprogramming from M1 to M2 phenotype, and the released Dex significantly reduced the oxidative damage. Various in vitro and in vivo assessments have confirmed that D@ApoEV\n                    <jats:sup>FasL<\/jats:sup>\n                    \u2229L can effectively regulate neutrophils, macrophages, and ROS, trigger an immune cascade, and restore intra\u2010articular immune homeostasis, exhibiting an effective RAM reconstruction ability and a promising therapeutic effect for RA.\n                  <\/jats:p>","DOI":"10.1002\/adma.202508072","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T11:21:42Z","timestamp":1759490502000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Engineered Apoptotic Extracellular Vesicles for Programmable Regulation of Neutrophil\u2010Macrophage\u2010ROS Pathogenic Axis to Reconstruct Rheumatoid Arthritis Microenvironment"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6319-6430","authenticated-orcid":false,"given":"Yaqing","family":"Kang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Rare Earth Resource Utilization &amp; 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