{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T06:47:20Z","timestamp":1793170040206,"version":"4.5.0"},"reference-count":203,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T00:00:00Z","timestamp":1732147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2023-00280923"],"award-info":[{"award-number":["RS-2023-00280923"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["22A0204L1"],"award-info":[{"award-number":["22A0204L1"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Korean Fund for Regenerative Medicine","award":["RS-2023-00280923"],"award-info":[{"award-number":["RS-2023-00280923"]}]},{"name":"Korean Fund for Regenerative Medicine","award":["22A0204L1"],"award-info":[{"award-number":["22A0204L1"]}]},{"name":"Ministry of Science and ICT","award":["RS-2023-00280923"],"award-info":[{"award-number":["RS-2023-00280923"]}]},{"name":"Ministry of Science and ICT","award":["22A0204L1"],"award-info":[{"award-number":["22A0204L1"]}]},{"name":"Ministry of Health and Welfare","award":["RS-2023-00280923"],"award-info":[{"award-number":["RS-2023-00280923"]}]},{"name":"Ministry of Health and Welfare","award":["22A0204L1"],"award-info":[{"award-number":["22A0204L1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Ischemic stroke (IS) remains a leading cause of mortality and long-term disability worldwide, with limited therapeutic options available. Despite the success of early interventions, such as tissue-type plasminogen activator administration and mechanical thrombectomy, many patients continue to experience persistent neurological deficits. The pathophysiology of IS is multifaceted, encompassing excitotoxicity, oxidative and nitrosative stress, inflammation, and blood\u2013brain barrier disruption, all of which contribute to neural cell death, further complicating the treatment of IS. Recently, extracellular vesicles (EVs) secreted naturally by various cell types have emerged as promising therapeutic agents because of their ability to facilitate selective cell-to-cell communication, neuroprotection, and tissue regeneration. Furthermore, engineered EVs, designed to enhance targeted delivery and therapeutic cargo, hold the potential to improve their therapeutic benefits by mitigating neuronal damage and promoting neurogenesis and angiogenesis. This review summarizes the characteristics of EVs, the molecular mechanisms underlying IS pathophysiology, and the emerging role of EVs in IS treatment at the molecular level. This review also explores the recent advancements in EV engineering, including the incorporation of specific proteins, RNAs, or pharmacological agents into EVs to enhance their therapeutic efficacy.<\/jats:p>","DOI":"10.3390\/pharmaceutics16121492","type":"journal-article","created":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T06:11:54Z","timestamp":1732169514000},"page":"1492","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Molecular Targeting of Ischemic Stroke: The Promise of Na\u00efve and Engineered Extracellular Vesicles"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9667-0086","authenticated-orcid":false,"given":"Jihun","family":"Lee","sequence":"first","affiliation":[{"name":"Laboratory of Stem Cells and Tissue Regeneration, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongho","family":"Geum","sequence":"additional","affiliation":[{"name":"Department of Medical Science, College of Medicine, Korea University, Seoul 02841, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Hyuk","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Anam Hospital, College of Medicine, Korea University, Seoul 02841, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3419-0538","authenticated-orcid":false,"given":"Jong-Hoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cells and Tissue Regeneration, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1161\/STR.0b013e318296aeca","article-title":"An updated definition of stroke for the 21st century: A statement for healthcare professionals from the American Heart Association\/American Stroke Association","volume":"44","author":"Sacco","year":"2013","journal-title":"Stroke"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/S1474-4422(21)00252-0","article-title":"Global, regional, and national burden of stroke and its risk factors, 1990-2019: A systematic analysis for the Global Burden of Disease Study 2019","volume":"20","author":"Collaborators","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1016\/S0140-6736(24)00757-8","article-title":"Global incidence, prevalence, years 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