{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T06:09:26Z","timestamp":1778479766307,"version":"3.51.4"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Recombinant tissue-type plasminogen activator (rtPA) is the only FDA-approved thrombolytic agent for acute ischemic stroke, yet its clinical utility is constrained by a narrow therapeutic time window, rapid clearance, and hemorrhagic transformation risk. Here, we developed a biomimetic nanothrombolytic comprising rtPA-conjugated, platelet-membrane-coated PLGA nanoparticles loaded with perfluorohexane (PNP-rtPA) to improve thrombus specificity and vascular safety. PNP-rtPA preserved rtPA enzymatic activity, achieved efficient fibrin clot lysis\n                    <jats:italic>in vitro<\/jats:italic>\n                    , and markedly enhanced thrombolysis in an electrical-stimulation-induced carotid thrombosis model. Using a refined proximal photothrombotic middle cerebral artery (MCA) occlusion mouse model that generates stable large-vessel thrombosis, we show that PNP-rtPA restored cerebral blood flow more effectively than free rtPA, reduced infarct volume, improved neurological outcomes, and increased short-term survival. Pharmacokinetic and imaging analyses demonstrated prolonged circulation and enhanced accumulation of PNP-rtPA in the injured cerebrovascular bed. Importantly, PNP-rtPA mitigated blood\u2013brain barrier (BBB) disruption, preserved tight junction and basement membrane integrity, and reduced hemorrhagic transformation and edema. Correspondingly, astrocytic swelling, microglial activation, and systemic cytokine release were attenuated, indicating improved neurovascular protection. Together, these results establish platelet-membrane cloaking and nanoscale rtPA delivery as an effective strategy to reconcile thrombolytic efficacy with vascular safety. PNP-rtPA represents a translatable biomimetic platform for achieving precise and safe thrombolysis in ischemic vascular disease.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1825954","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T05:30:00Z","timestamp":1778477400000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Platelet-membrane-coated nanoparticles enable safe and targeted thrombolysis with preserved neurovascular integrity"],"prefix":"10.3389","volume":"17","author":[{"given":"Ziying","family":"Feng","sequence":"first","affiliation":[{"name":"State Key Laboratory of Biomedical Imaging Science and System, Guangdong-Hong Kong Joint Laboratory for Metabolic Medicine, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences","place":["Shenzhen, Guangdong, China"]},{"name":"Neuroscience Research Center, Stroke Center, Department of Neurology, The First Hospital of Jilin University","place":["Changchun, Jilin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ogunleye Femi","family":"Abiola","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biomedical Imaging Science and System, Guangdong-Hong Kong Joint Laboratory for Metabolic Medicine, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences","place":["Shenzhen, Guangdong, China"]},{"name":"University of Chinese Academy of Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guojun","family":"Huang","sequence":"additional","affiliation":[{"name":"University of Chinese Academy of Sciences","place":["Beijing, China"]},{"name":"Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences","place":["Shenzhen, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianfang","family":"Kang","sequence":"additional","affiliation":[{"name":"University of Chinese Academy of Sciences","place":["Beijing, China"]},{"name":"Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences","place":["Shenzhen, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Karolinska Institutet","place":["Stockholm, Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Gong","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences","place":["Shenzhen, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junlei","family":"Chang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biomedical Imaging Science and System, Guangdong-Hong Kong Joint Laboratory for Metabolic Medicine, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences","place":["Shenzhen, Guangdong, China"]},{"name":"Neuroscience Research Center, Stroke Center, Department of Neurology, The First Hospital of Jilin University","place":["Changchun, Jilin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Pan","sequence":"additional","affiliation":[{"name":"University of Chinese Academy of Sciences","place":["Beijing, China"]},{"name":"Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences","place":["Shenzhen, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yinzhong","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biomedical Imaging Science and System, Guangdong-Hong Kong Joint Laboratory for Metabolic Medicine, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences","place":["Shenzhen, Guangdong, China"]},{"name":"University of Chinese Academy of Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"7517","DOI":"10.2147\/IJN.S333657","article-title":"Potential of nanocarrier-based drug delivery systems for brain targeting: a current review of literature","volume":"16","author":"Alotaibi","year":"2021","journal-title":"Int. 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