{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T19:58:09Z","timestamp":1789588689050,"version":"build-2803163510"},"reference-count":31,"publisher":"American Association for the Advancement of Science (AAAS)","content-domain":{"domain":["spj.science.org"],"crossmark-restriction":true},"short-container-title":["Biomater Res"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>Current pharmacological treatments for cardiac fibrosis are often limited by their efficacy and specificity, leading to marked side effects. Fibroblast activation protein (FAP) is specifically expressed on activated myofibroblasts (myoFbs) but not on resting cardiac fibroblasts, making it a promising target for cardiac fibrosis therapy. In this study, we engineered extracellular vesicles (EVs) conjugated with an anti-FAP single-chain variable fragment, termed \u03b1FAP-EVs, which specifically target myoFbs. Our results demonstrated that \u03b1FAP-EVs successfully targeted activated myoFbs in\u00a0vitro and localized to fibrotic regions in isoproterenol-induced mouse hearts in\u00a0vivo. To further enhance delivery efficiency, \u03b1FAP-EVs were combined with clodronate-loaded liposomes (\u03b1FAP-EL@CLD) to reduce liver accumulation and improve cardiac fibrotic site targeting. \u03b1FAP-EL@CLD loaded with cholesterol-methylated- and phosphorothioate-modified miR-29b (Agomir-29b) or the transforming growth factor beta 1 receptor inhibitor GW788388 significantly inhibited myoFb activation and reduced fibrosis in isoproterenol-induced mouse models. Importantly, these drug-loaded \u03b1FAP-EL@CLD vesicles exhibited high therapeutic efficacy with minimal systemic toxicity, attributed to their stability and targeted delivery capabilities. These findings suggest that \u03b1FAP-EL@CLD vesicles are promising candidates for cardiac fibrosis therapy, offering a foundation for future clinical applications.<\/jats:p>","DOI":"10.34133\/bmr.0179","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T17:38:01Z","timestamp":1742405881000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":13,"title":["Myofibroblast-Targeting Extracellular Vesicles: A Promising Platform for Cardiac Fibrosis Drug Delivery"],"prefix":"10.34133","volume":"29","author":[{"given":"Yi","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Biology and Medical Sciences, \rSoochow University, Suzhou 215123, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Institute of Biology and Medical Sciences, \rSoochow University, Suzhou 215123, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, \rThe First Affiliated Hospital of Wannan Medical College, Wuhu 241001, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Urology, Changhai Hospital, \rNaval Medical University, Shanghai 200433, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Department of Orthopedics of the Second Affiliated Hospital, \rZhejiang University School of Medicine, Hangzhou 310058, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection and School for Radiological and Interdisciplinary Sciences (RAD-X), \rSoochow University, Suzhou 125123, Jiangsu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuege","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Biology and Medical Sciences, \rSoochow University, Suzhou 215123, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Shen","sequence":"additional","affiliation":[{"name":"Institute of Biology and Medical Sciences, \rSoochow University, Suzhou 215123, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiapeng","family":"Gao","sequence":"additional","affiliation":[{"name":"Institute of Biology and Medical Sciences, \rSoochow University, Suzhou 215123, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Biology and Medical Sciences, \rSoochow University, Suzhou 215123, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Biology and Medical Sciences, \rSoochow University, Suzhou 215123, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijian","family":"Cai","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Department of Orthopedics of the Second Affiliated Hospital, \rZhejiang University School of Medicine, Hangzhou 310058, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, \rThe First Affiliated Hospital of Anhui Medical University, Hefei 230032, Anhui, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9305-9129","authenticated-orcid":true,"given":"Min","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Biology and Medical Sciences, \rSoochow University, Suzhou 215123, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2025,4,11]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab892"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2012.10.002"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2938-9"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021119-034527"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1504848"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.306565"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.05.004"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2017.57"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2006.11.001"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1546-z"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-021-00931-2"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2020.04.004"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12265-022-10284-3"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12030"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2021.120761"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-13-0027"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202400845"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13105-021-00814-z"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2019.06.004"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1532\/hsf.2079"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.201902099"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5002717"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm0509905"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.3317\/jraas.2005.006"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e3282f56ba5"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2009.05.002"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.7150\/thno.20524"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.70025"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2015.08.016"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1080\/21691401.2018.1501381"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2019.10.002"}],"container-title":["Biomaterials Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/spj.science.org\/doi\/pdf\/10.34133\/bmr.0179","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T08:00:29Z","timestamp":1744358429000},"score":1,"resource":{"primary":{"URL":"https:\/\/spj.science.org\/doi\/10.34133\/bmr.0179"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":31,"alternative-id":["10.34133\/bmr.0179"],"URL":"https:\/\/doi.org\/10.34133\/bmr.0179","relation":{},"ISSN":["2055-7124"],"issn-type":[{"value":"2055-7124","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1]]},"assertion":[{"value":"2024-09-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-06","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"0179"}}