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To address these, a NIR\u2010triggered nanoplatform (Cu(I)\u2010TA@HG) is developed for precise Cu(I) delivery to metastatic nasopharyngeal carcinoma (NPC) cells, thereby inducing potent cuproptosis. Drawing inspiration from the critical role of membrane proteins in cancer metastasis, tumor\u2010homing nanovesicles derived from GAS6\u2010overexpressing cell membranes (HG\u2010CMs) are engineered. These membranes exhibit enhanced affinity for the AXL receptor, which is frequently overexpressed in metastatic NPC. The HG\u2010CMs encapsulated cuprous\u2010loaded nanoparticles (Cu(I)\u2010TA), facilitating specific recognition via the GAS6\u2010AXL axis and promoting highly targeted NPC delivery while minimizing off\u2010target effects. Upon reaching the tumor, the Cu(I)\u2010TA@HG can effectively trigger cuproptosis through the synergistic effect originating from the GAS6\u2010AXL axis\u2010directed cell targeting and TA\u2010interfering copper ion excretion. Crucially, in vivo experiments demonstrate that this nanoplatform not only eradicates primary tumor sites but also effectively eliminates early metastatic lesions, leading to significant suppression of lung metastasis in an NPC model. This work establishes a strategic foundation for the rational design of nanotherapeutics that exploit cuproptosis for the treatment of aggressive and metastatic cancers.<\/jats:p>","DOI":"10.1002\/smll.202511219","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T14:07:46Z","timestamp":1765807666000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Homing Effect Directed Cuprous Delivery Activates Cuproptosis Against Nasopharyngeal Carcinoma and Metastasis"],"prefix":"10.1002","volume":"22","author":[{"given":"You","family":"Zou","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery Renmin Hospital of Wuhan University  238 Jie\u2010Fang Road Wuhan Hubei 430060 P. R. 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