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Mesenchymal stromal cells (MSCs) hold therapeutic promise for ALF because of their immunomodulatory and tissue\u2010repair capacities. However, in the ALF inflammatory microenvironment, characterized by abundant activated M1 macrophages and elevated pro\u2010inflammatory cytokines, MSCs are susceptible to apoptosis, resulting in low survival and limited therapeutic efficacy. Here, we combined the anti\u2010inflammatory small\u2010molecule rosiglitazone with MSCs to construct a cell\u2013drug conjugate (CDC) using MSCs as cellular carriers. Rosiglitazone was encapsulated within nanoparticles coated with neutrophil membranes and anchored onto the MSC surface. Sustained release of rosiglitazone from the MSC surface intrinsically enhanced MSC proliferation and paracrine activity through PI3K\u2013Akt pathway activation and extrinsically modulated the inflammatory microenvironment by promoting macrophage polarization toward an anti\u2010inflammatory phenotype. In a mouse model of ALF, rosiglitazone nanoparticle\u2010modified MSCs exhibited enhanced accumulation and prolonged retention in the injured liver, more effectively inhibited hepatocyte apoptosis and promoted hepatocyte proliferation, thereby achieving superior therapeutic efficacy. Thus, our study provides a promising strategy for enhancing MSC\u2010based therapy in ALF.<\/jats:p>","DOI":"10.1002\/advs.77411","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T15:04:51Z","timestamp":1787670291000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mesenchymal Stromal Cell\u2010Based Cell\u2013Drug Conjugates for the Treatment of Acute Liver Failure"],"prefix":"10.1002","author":[{"given":"Tenghui","family":"Ye","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences and Engineering Guangzhou International Campus South China University of Technology  Guangzhou People's Republic of China"},{"name":"National Engineering Research Center for Tissue Restoration and Reconstruction South China University of Technology  Guangzhou People's Republic of China"},{"name":"Guangdong Province Key Laboratory of Biomedical Engineering South China University of 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