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In this regard, multipathway\u2010assisted mesenchymal stem cell\u2010derived nanovesicles (stemsomes) offer a promising universal platform for overcoming the unmet needs of lung cancer therapeutics, particularly for patients lacking identifiable oncogenic drivers. This study introduces a novel strategy in which dexamethasone, a compound conventionally used as an anti\u2010inflammatory drug, is repurposed to enhance the tumor\u2010targeting capabilities of stemsomes. Nanoparticles engineered by fusing these dexamethasone\u2010primed stemsomes with liposomes exhibit markedly improved therapeutic effects. According to transcriptomic and siRNA\u2010mediated knockdown experiments, this enhanced targeting of tumor cells is driven by the dexamethasone\u2010induced upregulation of key cell adhesion proteins, specifically ephrin type\u2010A receptor 2 and neurogenic locus notch homolog protein 3. 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These findings indicate the discovery of a highly translational and mutation\u2010independent strategy that represents a promising novel mechanism for engineering vesicle surfaces for NSCLC therapy.<\/jats:p>","DOI":"10.1002\/advs.76039","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T19:56:32Z","timestamp":1781034992000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Surfaceome Reprogramming of Stemsomes Promotes Lung Cancer Targeting via Potentiated Receptor\u2013Ligand Interactions"],"prefix":"10.1002","volume":"13","author":[{"given":"Geunhye","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Health Sciences and Technology GAIHST Gachon University  Incheon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In Ah","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Health Sciences and Technology GAIHST Gachon University  Incheon South Korea"},{"name":"Ectosome Inc.  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