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Simvastatin (Sim) can modulate endothelial function by increasing endothelial nitric oxide synthase (eNOS)\u2010dependent nitric oxide (NO) release, thereby reversing capillarization and attenuating liver fibrosis. However, monotherapy often demonstrates limited therapeutic effectiveness given the complex pathophysiology of liver fibrosis. Herein, a type of multifunctional liposomal microbubbles (MBs) carrying both Sim and platelet membrane (PM) has been designed for drug delivery targeting the inflammatory LSECs, with ultrasound\u2010targeted microbubble destruction (UTMD) to mediate efficient release of these therapeutic agents inside the liver sinusoidal. In rat liver fibrosis model, the multifunctional MBs reverses capillarization through the increase of eNOS\u2010dependent NO production. Subsequently, the MBs adhering to the inflammatory LSECs block the adhesion and activation of inherent platelet (PLT), thereby decreasing platelet\u2010derived growth factor \u03b2 (PDGF\u2010\u03b2) to inhibit the HSCs activation. This study demonstrates the strong therapeutic efficacy of the multifunctional MBs integrating Sim and PLT against liver fibrosis, which highlights a great potential for effectively managing this intractable chronic disease.<\/jats:p>","DOI":"10.1002\/adhm.202500196","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T07:27:19Z","timestamp":1744097239000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Ultrasound\u2010Mediated Biomimetic Microbubbles Effectively Reverse LSECs Capillarization and Exert Antiplatelet Therapy in Liver Fibrosis"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4590-7701","authenticated-orcid":false,"given":"Huan","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Medical Ultrasound Laboratory of Novel Optoacoustic (Ultrasonic) imaging The Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou 510630 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huolin","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Medical Ultrasound Laboratory of Novel Optoacoustic (Ultrasonic) imaging The Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou 510630 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Medical Ultrasound Laboratory of Novel Optoacoustic (Ultrasonic) imaging The Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou 510630 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujia","family":"You","sequence":"additional","affiliation":[{"name":"Department of Medical Ultrasound Laboratory of Novel Optoacoustic (Ultrasonic) imaging The Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou 510630 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Miao","sequence":"additional","affiliation":[{"name":"Department of Medical Ultrasound Laboratory of Novel Optoacoustic (Ultrasonic) imaging The Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou 510630 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medical Ultrasound Laboratory of Novel Optoacoustic (Ultrasonic) imaging The Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou 510630 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Leng","sequence":"additional","affiliation":[{"name":"Department of Medical Ultrasound Laboratory of Novel Optoacoustic (Ultrasonic) imaging The Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou 510630 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongqin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Medical Ultrasound Laboratory of Novel Optoacoustic (Ultrasonic) imaging The Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou 510630 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4271-0310","authenticated-orcid":false,"given":"Xintao","family":"Shuai","sequence":"additional","affiliation":[{"name":"Nanomedicine Research Center The Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou 510630 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Medical Ultrasound Laboratory of Novel Optoacoustic (Ultrasonic) imaging The Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou 510630 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tinghui","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Medical Ultrasound Laboratory of Novel Optoacoustic (Ultrasonic) imaging The Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou 510630 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,8]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-011110-130246"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2023.01.052"},{"key":"e_1_2_9_3_1","first-page":"344","volume":"3","author":"Weiskirchen R.","year":"2014","journal-title":"Hepatobil. 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