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In this study, sEVs with enriched integrin \u03b24, designated as XP\u2010ITG\u03b24\u2010sEV, are engineered to enhance lung\u2010targeting capabilities. The therapeutic efficacy of doxorubicin\u2010loaded XP\u2010ITG\u03b24\u2010sEV (XP\u2010ITG\u03b24\u2010sEV\/Dox) is evaluated in targeting pulmonary metastasis of advanced hepatocellular carcinoma (HCC) using a murine lung metastasis model. Remarkably, treatment with XP\u2010ITG\u03b24\u2010sEV\/Dox effectively suppresses tumor cell colonization in the lungs compared to an equivalent dose of free doxorubicin. Histological analyses reveal a reduction in lung metastatic foci, inhibition of proliferation, and an increase in apoptosis of HCC cells. Notably, XP\u2010ITG\u03b24\u2010sEV\/Dox exhibits a superior therapeutic efficacy with an improved safety profile compared to a higher dose of free doxorubicin that demonstrates similar efficacy. These findings collectively underscore the potential of integrin \u03b24\u2010enriched sEVs as a targeted drug delivery system for addressing pulmonary metastasis of HCC.<\/jats:p>","DOI":"10.1002\/adhm.202502649","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T07:11:11Z","timestamp":1752477071000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrin \u03b24\u2010Enriched Small Extracellular Vesicle as Drug Delivery Vehicle for Targeting Pulmonary Metastasis of Hepatocellular Carcinoma"],"prefix":"10.1002","volume":"14","author":[{"given":"Tung Him","family":"Ng","sequence":"first","affiliation":[{"name":"Department of Pathology School of Clinical Medicine Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong 510282 P. R. 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