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Fibroblast activation protein (FAP), highly expressed by activated HSCs, is a pivotal player in the pathogenesis of liver fibrosis. Delineating the mechanisms underlying HSC activation and devising strategies to curb their hyperactivity are paramount for the management and prevention of liver fibrosis. In this study, we explored a pioneering therapeutic approach leveraging CD163 antibody-conjugated liposomal nanoparticles (LNPs) encapsulating FAP-specific chimeric antigen receptor macrophage (CAR-M) mRNA (\u03b1CD163\/LNP-FAPCAR). These LNPs are designed to selectively transduce liver macrophages, facilitating the in situ generation of FAP-specific CAR-modified macrophages (FAPCAR-M). Our findings revealed that these LNPs efficiently transduced macrophages, augmenting their phagocytic capabilities toward target cells. This resulted in a significant reduction of ECM and a concomitant enhancement of liver fibrosis resolution. The overarching goal is to precisely target and neutralize hyperactive fibroblasts, offering a promising avenue for treating liver fibrosis.<\/jats:p>","DOI":"10.1073\/pnas.2534673123","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T17:39:58Z","timestamp":1780076398000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":2,"title":["mRNA-laden LNP-enabled in situ CAR-macrophage alleviates liver fibrosis via inhibiting activated HSCs and modulating the immune microenvironment"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5192-4906","authenticated-orcid":false,"given":"Xin","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Family Medicine, Shengjing Hospital of China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2467-7345","authenticated-orcid":false,"given":"Junfeng","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Shengjing Hospital of China Medical University","place":["Shenyang, China"]},{"id":[{"id":"https:\/\/ror.org\/04k5rxe29","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Nephrology, and Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-communicable Diseases, Affiliated Hospital of Guangdong Medical University","place":["Zhanjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7433-3903","authenticated-orcid":false,"given":"Shuo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shengjing Hospital of China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4273-6625","authenticated-orcid":false,"given":"Botian","family":"Deng","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04k5rxe29","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Nephrology, and Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-communicable Diseases, Affiliated Hospital of Guangdong Medical University","place":["Zhanjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5184-3129","authenticated-orcid":false,"given":"Peng","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04k5rxe29","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Nephrology, and Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-communicable Diseases, Affiliated Hospital of Guangdong Medical University","place":["Zhanjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5458-4787","authenticated-orcid":false,"given":"Qiuyu","family":"Zhao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/030e3n504","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Key Laboratory of Ministry of Education for Traditional Chinese Medicine Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3129-3710","authenticated-orcid":false,"given":"Hongbo","family":"Liu","sequence":"additional","affiliation":[{"name":"Third Department of Respiratory, Shengjing Hospital of China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6206-8404","authenticated-orcid":false,"given":"Jiahe","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Shengjing Hospital of China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.09.014"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2020.111556"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2022.12.005"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells9092027"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-020-09909-3"},{"key":"e_1_3_4_6_2","first-page":"0282","article-title":"Development and characterization of novel FAP-Targeted theranostic pairs: A bench-to-bedside study","volume":"6","author":"Huang W.","year":"2023","unstructured":"W. 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