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However, there is still no effective strategy to regulate macrophages because of the difficulty and complexity of macrophage inflammatory phenotypic modulation and the insufficient therapeutic efficacy caused by the extracellular matrix (ECM) barrier. Here, AC73 and siUSP1 dual drug\u2010loaded lipid nanoparticle is designed to carry milk fat globule epidermal growth factor 8 (MFG\u2010E8) (named MUA\/Y) to effectively inhibit macrophage proinflammatory signals and degrade the ECM barrier. MFG\u2010E8 is released in response to the high reactive oxygen species (ROS) environment in LF, transforming macrophages from a proinflammatory (M1) to an anti\u2010inflammatory (M2) phenotype and inducing macrophages to phagocytose collagen. Collagen ablation increases AC73 and siUSP1 accumulation in hepatic stellate cells (HSCs) and inhibits HSCs overactivation. Interestingly, complete resolution of liver inflammation, significant collagen degradation, and HSCs deactivation are observed in methionine choline deficiency (MCD) and CCl\n                    <jats:sub>4<\/jats:sub>\n                    models after tail vein injection of MUA\/Y. Overall, this work reveals a macrophage\u2010focused regulatory treatment strategy to eliminate LF progression at the source, providing a new perspective for the clinical treatment of advanced LF.\n                  <\/jats:p>","DOI":"10.1002\/advs.202306899","type":"journal-article","created":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T12:04:08Z","timestamp":1702037048000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["An Autologous Macrophage\u2010Based Phenotypic Transformation\u2010Collagen Degradation System Treating Advanced Liver Fibrosis"],"prefix":"10.1002","volume":"11","author":[{"given":"Bo\u2010Wen","family":"Duan","sequence":"first","affiliation":[{"name":"State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing 210009 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan\u2010Jun","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing 210009 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue\u2010Na","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing 210009 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng\u2010Meng","family":"Han","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing 210009 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao\u2010Yuan","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing 210009 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He\u2010Yuan","family":"Hong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing 210009 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling\u2010Feng","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing 210009 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Xing","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing 210009 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1620-1777","authenticated-orcid":false,"given":"Hu\u2010Lin","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing 210009 China"},{"name":"Jiangsu Key Laboratory of Druggability of Biopharmaceuticals China Pharmaceutical University  Nanjing 210009 China"},{"name":"Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases China Pharmaceutical University  Nanjing 210009 China"},{"name":"NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients China Pharmaceutical University  Nanjing 210009 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,8]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30411-7"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.01.046"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29361"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2023.03.005"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2020.04.011"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2017.05.007"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000362"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13498"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2022.07.018"},{"key":"e_1_2_8_8_3","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-020-00836-6"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2019.105765"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI98156"},{"key":"e_1_2_8_11_1","volume":"109","author":"Prakash Ramachandrana A. 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