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Here, it is found that the vascular cell adhesion molecule\u20101 (VCAM1) is highly overexpressed in the vascular cells of BSSI. It is proposed that the combination of VCAM1\u2010mediated transcytosis and ultrasonic cavitation can consecutively overcome the biological barriers of vascular endothelial cells and EPS for biofilm eradication. To demonstrate the feasibility, a VCAM1\u2010targeted and ultrasound (US)\u2010activated liposome (LPCOTML) loaded with a reactive\u2010oxygen\u2010species (ROS)\u2010responsive lipoid prodrug of oleoyl meropenem, sonosensitizer of lipoid Ce6, and perfluoropentane is developed. LPCOTML can recognize the receptors on vascular cells, and initiate receptor\u2010mediated transcytosis for transendothelial transport into the BSSI periphery. LPCOTML subsequently transforms from nanoparticle into microbubble via liquid\u2013gas phase transition under US irradiation, triggering strong ultrasonic cavitation to blow up the EPS and deeply penetrate the biofilms. The sonosensitizer Ce6 induces ROS production under US irradiation and triggers the release of meropenem to induce potent antibacterial effect in a BSSI model. This study presents an effective strategy to tackle the biological barriers in BSSI via combining receptor\u2010mediated transcytosis and ultrasonic cavitation.<\/jats:p>","DOI":"10.1002\/adma.202411092","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T02:50:43Z","timestamp":1730083843000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Transcytosable and Ultrasound\u2010Activated Liposome Enables Deep Penetration of Biofilm for Surgical Site Infection Management"],"prefix":"10.1002","volume":"37","author":[{"given":"Guowei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Ultrasound in Medicine The Second Affiliated Hospital of Zhejiang University School of Medicine Zhejiang University  Hangzhou 310009 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