{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:27:34Z","timestamp":1787318854631,"version":"build-2736575974"},"reference-count":31,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,4,27]],"date-time":"2024-04-27T00:00:00Z","timestamp":1714176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council","award":["MOST 111-2811-M-182-002"],"award-info":[{"award-number":["MOST 111-2811-M-182-002"]}]},{"name":"National Science and Technology Council","award":["NSTC 111-2124-M-182-001"],"award-info":[{"award-number":["NSTC 111-2124-M-182-001"]}]},{"name":"National Science and Technology Council","award":["CMRPD1H0363"],"award-info":[{"award-number":["CMRPD1H0363"]}]},{"name":"National Science and Technology Council","award":["BMRP466"],"award-info":[{"award-number":["BMRP466"]}]},{"DOI":"10.13039\/501100004606","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["MOST 111-2811-M-182-002"],"award-info":[{"award-number":["MOST 111-2811-M-182-002"]}],"id":[{"id":"10.13039\/501100004606","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004606","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["NSTC 111-2124-M-182-001"],"award-info":[{"award-number":["NSTC 111-2124-M-182-001"]}],"id":[{"id":"10.13039\/501100004606","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004606","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPD1H0363"],"award-info":[{"award-number":["CMRPD1H0363"]}],"id":[{"id":"10.13039\/501100004606","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004606","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["BMRP466"],"award-info":[{"award-number":["BMRP466"]}],"id":[{"id":"10.13039\/501100004606","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Plasminogen activators, such as recombinant tissue-type plasminogen activators (rtPAs), while effective in treating thromboembolic diseases, often induce hemorrhagic complications due to non-specific enzyme activities in the systemic circulation. This study evaluated the targeting efficiency, efficacy, biodistribution, and potential toxicity of a rtPA covalently attached to chitosan-coated magnetic nanoparticles (chitosan-MNP-rtPA). The thrombolytic activity of a chitosan-MNP-rtPA was preserved by protection from an endogenous plasminogen activator inhibitor-1 (PAI-1) in whole blood and after circulation in vivo, as examined by thromboelastometry. Single-photon emission computed tomography (SPECT) demonstrated real-time retention of a 99mTc-MNP-rtPA induced by magnet application in a rat embolic model; an 80% reduction in rtPA dosage for a chitosan-MNP-rtPA with magnetic guidance was shown to restore blood flow. After treatment, iron deposition was observed in the reticuloendothelial systems, with portal edema and neutrophil infiltration in the liver at a ten-fold higher dose but not the regular dose. Nevertheless, no liver or renal toxicity was observed at this higher dose. In conclusion, the liver may still be the major deposit site of rtPA nanocomposites after targeted delivery; chitosan-coated MNPs are potentially amenable to target therapeutics with parenteral administration.<\/jats:p>","DOI":"10.3390\/pharmaceutics16050596","type":"journal-article","created":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T03:57:56Z","timestamp":1714622276000},"page":"596","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Targeted Thrombolysis with Magnetic Nanotherapeutics: A Translational Assessment"],"prefix":"10.3390","volume":"16","author":[{"given":"Ming-Lu","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Physiology & Pharmacology, College of Medicine, Chang Gung University, Guishan, Taoyuan 33302, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siao-Yun","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Physiology & Pharmacology, College of Medicine, Chang Gung University, Guishan, Taoyuan 33302, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6527-4801","authenticated-orcid":false,"given":"Jyh-Ping","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Chemical and Materials Engineering, College of Engineering, Chang Gung University, Guishan, Taoyuan 33302, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ching","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Physiology & Pharmacology, College of Medicine, Chang Gung University, Guishan, Taoyuan 33302, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Ming","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Pathology, Chang Gung Memorial Hospital, Guishan, Taoyuan 33305, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7222-2601","authenticated-orcid":false,"given":"Shiaw-Pyng","family":"Wey","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging and Radiological Sciences, Chang Gung University, Guishan, Taoyuan 33302, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Chang Gung Memorial Hospital, Guishan, Taoyuan 33305, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0481-1180","authenticated-orcid":false,"given":"Yunn-Hwa","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Physiology & Pharmacology, College of Medicine, Chang Gung University, Guishan, Taoyuan 33302, Taiwan"},{"name":"Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Guishan, Taoyuan 33305, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e46","DOI":"10.1161\/STROKEAHA.118.020176","article-title":"2018 Guidelines for the early management of patients with acute ischemic stroke: A guideline for healthcare professionals from the American Heart Association\/American Stroke Association","volume":"49","author":"Furie","year":"2018","journal-title":"Stroke"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/j.1538-7836.2004.00827.x","article-title":"Pleiotropic functions of plasminogen activator inhibitor-1","volume":"3","author":"Lijnen","year":"2005","journal-title":"J. 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