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Guided by this process\u2010level logic, we engineered a multiarmed nanovesicle, termed tPA@CTG, that integrates CREKA\u2010mediated thrombus targeting, thrombin\u2010responsive activation, localized tissue plasminogen activator release, and MRI monitoring. tPA@CTG achieves efficient thrombus targeting under both static and flow conditions, along with thrombin\u2010triggered structural activation and localized tPA release. In a rat carotid artery thrombosis model, tPA@CTG restores near\u2010complete recanalization with a thrombolytic efficiency of 99.5 \u00b1 0.6% and blood flow recovery of 95.1 \u00b1 2.5%, substantially outperforming free tPA. Remarkably, even at half the dose, tPA@CTG remains more effective than full\u2010dose free tPA, highlighting the therapeutic benefit of combining thrombus targeting with thrombin\u2010responsive local release. Transcriptomic analysis reveals modulation of complement and coagulation pathways, indicating active remodeling of the thrombotic microenvironment beyond simple clot dissolution. Biosafety assessments confirm excellent biocompatibility and substantially reduced bleeding risk compared to free tPA. Together, tPA@CTG provides an integrated platform for targeted, thrombin\u2010responsive, and MRI\u2010monitored thrombolysis.<\/jats:p>","DOI":"10.1002\/adhm.71632","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T10:11:26Z","timestamp":1787220686000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Thrombin\u2010Responsive Multiarmed Nanovesicles for Targeted Delivery of Tissue Plasminogen Activator and MRI\u2010Monitored Thrombolysis"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4709-1264","authenticated-orcid":false,"given":"Yu","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Radiology Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai P. R. 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