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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,8,25]]},"abstract":"<jats:p>\n                    Hepatic fibrosis is a central pathological driver of chronic liver diseases, including metabolic dysfunction-associated steatotic liver disease and alcohol-related liver disease, which collectively impose a growing global health burden. Fibrosis is primarily mediated by persistent activation of hepatic stellate cells (aHSCs) and excessive deposition of stiff extracellular matrix (ECM). The dense and rigid ECM-aHSCs network severely hinders drug delivery and penetration, posing a major challenge for effective antifibrotic therapy. Here, we developed an aHSCs-targeted nanocomplex (AMD3100\/MnO\n                    <jats:sub>2<\/jats:sub>\n                    @BSA nanoparticles, AMB NPs) to remodel this rigid fibrotic barrier. This platform inhibits the fibrotic process by inducing cellular senescence and activating endogenous immune surveillance. Upon liver accumulation, AMB NPs preferentially recognize CXCR4 on aHSCs and subsequently release Mn\n                    <jats:sup>2+<\/jats:sup>\n                    to engage the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS\u2013STING) innate immune pathway, thereby robustly inducing cellular senescence, suppressing cell proliferation and reducing cellular stiffness. This process enhances the production of senescence-associated secretory phenotype factors, promotes collagen degradation and matrix loosening, and facilitates immune-mediated clearance of senescent aHSCs. These findings demonstrate the potent antifibrotic efficacy of AMB NPs and highlight a synergistic nanomedicine strategy that integrates aHSCs senescence induction, immune surveillance, and ECM remodeling, providing a rational therapeutic framework for hepatic fibrosis intervention.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2600215123","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T19:03:46Z","timestamp":1786993426000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["CXCR4-targeted dual softener for inducing senescence therapy in hepatic fibrosis"],"prefix":"10.1073","volume":"123","author":[{"given":"Junmei","family":"Mu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01sfm2718","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmaceutics, National Medical Products Administration Key Laboratory for Research and Evaluation of 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Sikk, S. Haldre, S. M. Aquilonius, P. Taba, Manganese-induced parkinsonism due to Ephedrone abuse. 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Mu CXCR4-targeted dual Softener for inducing senescence therapy in hepatic fibrosis. Dryad. https:\/\/doi.org\/10.5061\/dryad.rn8pk0psj. Deposited 29 July 2026."},{"key":"e_1_3_4_48_2","doi-asserted-by":"crossref","unstructured":"S. A. Hoang Gene expression predicts histological severity and reveals distinct molecular profiles of nonalcoholic fatty liver disease. GEO. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE130970. Accessed 15 August 2019.","DOI":"10.1038\/s41598-019-48746-5"},{"key":"e_1_3_4_49_2","unstructured":"T. Kodama Transcriptome profiling of human non-alcoholic fatty liver disease. GEO. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE167523. Accessed 31 May 2021."},{"key":"e_1_3_4_50_2","unstructured":"K. Bessho Comprehensive gene expression profile of human livers from patients with biliary atresia at the time of diagnosis and the corresponding disease and normal controls. GEO. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE46960. Accessed 1 June 2013."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2600215123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T19:04:33Z","timestamp":1786993473000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2600215123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,17]]},"references-count":50,"journal-issue":{"issue":"34","published-print":{"date-parts":[[2026,8,25]]}},"alternative-id":["10.1073\/pnas.2600215123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2600215123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,17]]},"assertion":[{"value":"2026-01-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2600215123"}}