{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T03:49:09Z","timestamp":1788320949973,"version":"build-2803163510"},"reference-count":78,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,2,18]],"date-time":"2024-02-18T00:00:00Z","timestamp":1708214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korea Research Foundation","award":["2022R1A2C1011348"],"award-info":[{"award-number":["2022R1A2C1011348"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Ischemic stroke-induced neuronal cell death leads to the permanent impairment of brain function. The Fas-mediating extrinsic apoptosis pathway and the cytochrome c-mediating intrinsic apoptosis pathway are two major molecular mechanisms contributing to neuronal injury in ischemic stroke. In this study, we employed a Fas-blocking peptide (FBP) coupled with a positively charged nona-arginine peptide (9R) to form a complex with negatively charged siRNA targeting Bax (FBP9R\/siBax). This complex is specifically designed to deliver siRNA to Fas-expressing ischemic brain cells. This complex enables the targeted inhibition of Fas-mediating extrinsic apoptosis pathways and cytochrome c-mediating intrinsic apoptosis pathways. Specifically, the FBP targets the Fas\/Fas ligand signaling, while siBax targets Bax involved in mitochondria disruption in the intrinsic pathway. The FBP9R carrier system enables the delivery of functional siRNA to hypoxic cells expressing the Fas receptor on their surface\u2014a finding validated through qPCR and confocal microscopy analyses. Through intranasal (IN) administration of FBP9R\/siCy5 to middle cerebral artery occlusion (MCAO) ischemic rat models, brain imaging revealed the complex specifically localized to the Fas-expressing infarcted region but did not localize in the non-infarcted region of the brain. A single IN administration of FBP9R\/siBax demonstrated a significant reduction in neuronal cell death by effectively inhibiting Fas signaling and preventing the release of cytochrome c. The targeted delivery of FBP9R\/siBax represents a promising alternative strategy for the treatment of brain ischemia.<\/jats:p>","DOI":"10.3390\/pharmaceutics16020290","type":"journal-article","created":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T10:40:15Z","timestamp":1708339215000},"page":"290","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Intranasal Delivery of Anti-Apoptotic siRNA Complexed with Fas-Signaling Blocking Peptides Attenuates Cellular Apoptosis in Brain Ischemia"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1504-317X","authenticated-orcid":false,"given":"Kunho","family":"Chung","sequence":"first","affiliation":[{"name":"Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Seoul 04763, Republic of Korea"},{"name":"Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7760-8693","authenticated-orcid":false,"given":"Irfan","family":"Ullah","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Seoul 04763, Republic of Korea"},{"name":"Department of Internal Medicine, Yale University, New Haven, CT 06520, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6660-5194","authenticated-orcid":false,"given":"Yujong","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Seoul 04763, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunhwa","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Seoul 04763, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4237-1621","authenticated-orcid":false,"given":"Gyeongju","family":"Yun","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Seoul 04763, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seoyoun","family":"Heo","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Seoul 04763, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minkyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Seoul 04763, Republic of 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Technology, Hanyang University, Seoul 04763, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0759-7631","authenticated-orcid":false,"given":"Taiyoun","family":"Rhim","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Seoul 04763, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1680-7218","authenticated-orcid":false,"given":"Sang-Kyung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Institute of Nanoscience and Technology, Hanyang University, Seoul 04763, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.gheart.2014.01.001","article-title":"The global burden of ischemic stroke: Findings of the GBD 2010 study","volume":"9","author":"Bennett","year":"2014","journal-title":"Glob. 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