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Activated hepatic stellate cells (aHSCs) are the principal drivers of fibrogenesis and therefore constitute key therapeutic targets. Lanifibranor, a pan\u2010peroxisome proliferator\u2010activated receptor agonist, has shown promising antifibrotic efficacy; however, its clinical application is limited by rapid systemic clearance and insufficient accumulation in fibrotic liver tissue. In this study, we report an aHSC\u2010targeted nanoplatform for lanifibranor delivery based on vitamin A\u2010functionalized two\u2010dimensional iron sulfide nanosheets (FeS\u2010V\n                    <jats:sub>A<\/jats:sub>\n                    @lanifibranor, FVL). Lanifibranor was electrostatically loaded onto vitamin A\u2010modified FeS nanosheets, enabling selective uptake by aHSCs and enhancing hepatic accumulation of lanifibranor. FVL significantly downregulated the expression of key fibrogenic markers and markedly reduced collagen accumulation. Mechanistically, the therapeutic efficacy of FVL arises from a dual\u2010action mechanism: inhibition of SMAD2\/3 phosphorylation within the transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2) signaling pathway and induction of ferroptosis in aHSCs. In conclusion, this study provides an effective aHSC\u2010specific nanotherapeutic strategy for liver fibrosis treatment and highlights the translational potential of FVL nanoplatforms for targeted antifibrotic therapy.\n                  <\/jats:p>","DOI":"10.1002\/adhm.71657","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T10:19:57Z","timestamp":1789121997000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Engineered Nanoplatforms Targeting Activated Hepatic Stellate Cells for Liver Fibrosis Therapy via TGF\u2010\u03b2 Axis Inhibition and Ferroptosis Induction"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7043-474X","authenticated-orcid":false,"given":"Yinuo","family":"Yang","sequence":"first","affiliation":[{"name":"Shandong Provincial Hospital Cheeloo College of Medicine Shandong University  Ji'nan Shandong 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