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This dysfunction arises from two key barriers: first, impaired recognition of apoptotic cells due to activation of the CD47\u2013SIRP\u03b1 immune checkpoint; and second, insufficient metabolic processing of apoptotic cell\u2010derived substrates, which limits the capacity for continual efferocytosis. Arg1\u2010mediated arginine metabolism has emerged as a crucial pathway supporting this process. To address these limitations, we created Am@SExo, a dual\u2010functional engineered exosome derived from macrophages that unites checkpoint inhibition with metabolic reprogramming. The vesicles overexpress SIRP\u03b1 on its surface to competitively engage CD47 on apoptotic cells and relieve the inhibitory signal, facilitating initial binding and uptake. Subsequently, it delivers Arg1 mRNA to recipient macrophages, driving an arginine to putrescine program aligned with Rac1 and actin remodeling to sustain successive rounds of clearance. In ApoE\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, systemic administration of Am@SExo significantly reduced necrotic core area, increased fibrous cap thickness, and enhanced features of plaque stability. Together, our findings demonstrate that Am@SExo as a single\u2010platform, dual\u2010phase modulator that restores macrophage continual efferocytosis, offering a promising strategy to resolve inflammation and stabilize atherosclerotic plaques.\n                  <\/jats:p>","DOI":"10.1002\/advs.75941","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T15:13:23Z","timestamp":1780586003000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Dual\u2010Phase Exosomal Nanotherapy Enhances Continual Efferocytosis by Coordinating Checkpoint Inhibition and Metabolic Reprogramming in Atherosclerosis"],"prefix":"10.1002","volume":"13","author":[{"given":"Danwen","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Cardiology Shanghai Institute of Cardiovascular Diseases Zhongshan Hospital Fudan University  Shanghai China"},{"name":"State Key Laboratory of Cardiovascular 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