A self-assembled DNA-nanoparticle with a targeting peptide for hypoxia-inducible gene therapy of ischemic stroke
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Oh, Jungju | - |
dc.contributor.author | Lee, Jaewon | - |
dc.contributor.author | Piao, Chunxian | - |
dc.contributor.author | Jeong, Ji Hoon | - |
dc.contributor.author | Lee, Minhyung | - |
dc.date.accessioned | 2021-07-30T05:23:06Z | - |
dc.date.available | 2021-07-30T05:23:06Z | - |
dc.date.created | 2021-05-12 | - |
dc.date.issued | 2019-05 | - |
dc.identifier.issn | 2047-4830 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/4575 | - |
dc.description.abstract | A self-assembled nanoparticle composed of hypoxia-specific anti-RAGE peptide (HSAP), heme oxygenase-1 plasmid (pHO1), and deoxycholate-conjugated polyethylenimine-2k (DP2k) was developed for ischemic stroke therapy. RAGE is over-expressed and induces inflammation in the ischemic brain. To inhibit RAGE-mediated signal transduction, HSAP was produced by recombinant DNA technology, based on the RAGE-binding domain of high mobility group box-1. Because of the specific binding to RAGE, the nanoparticle with HSAP (HSAP-NP) may have dual roles as a cytoprotective reagent and a specific ligand to RAGE for receptor-mediated transfection. As a cytoprotective reagent, the HSAP-NP reduced RAGE expression on the surface of the brain cells by inhibiting the positive feedback of RAGE-mediated signal transduction. As a result, inflammation, apoptosis, and reactive oxygen species were decreased in hypoxic cells. As a gene carrier, HSAP-NP showed a higher transfection efficiency than polyethylenimine-25k, DP2k, and Lipofectamine. Particularly, HSAP-NP enhanced gene delivery to hypoxic cells. In the stroke animal models, HSAP-NP reduced the levels of RAGE, inducible nitric oxide synthase, and inflammation. Additionally, HSAP-NP with pHO1 (HSAP-NP/pHO1) increased HO1 expression in the ischemic brain. Gene expression was higher in hypoxia-inducible factor-1 (HIF-1)-positive cells than in HIF-1-negative cells, suggesting that HSAP-NP delivered the genes to ischemic tissues more efficiently. Cell death and infarct volume in the stroke models were significantly decreased by HSAP-NP/pHO1 compared with HSAP alone or the DP2k/pHO1 complex. Therefore, HSAP-NP may be a useful gene and peptide therapy system for stroke therapy with dual functions of hypoxia-specific gene delivery and cytoprotective effects. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | ROYAL SOC CHEMISTRY | - |
dc.title | A self-assembled DNA-nanoparticle with a targeting peptide for hypoxia-inducible gene therapy of ischemic stroke | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Lee, Minhyung | - |
dc.identifier.doi | 10.1039/c8bm01621f | - |
dc.identifier.scopusid | 2-s2.0-85064934821 | - |
dc.identifier.wosid | 000466769000033 | - |
dc.identifier.bibliographicCitation | BIOMATERIALS SCIENCE, v.7, no.5, pp.2174 - 2190 | - |
dc.relation.isPartOf | BIOMATERIALS SCIENCE | - |
dc.citation.title | BIOMATERIALS SCIENCE | - |
dc.citation.volume | 7 | - |
dc.citation.number | 5 | - |
dc.citation.startPage | 2174 | - |
dc.citation.endPage | 2190 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Materials Science | - |
dc.relation.journalWebOfScienceCategory | Materials Science, Biomaterials | - |
dc.subject.keywordPlus | HEME OXYGENASE-1 GENE | - |
dc.subject.keywordPlus | RAGE-BINDING PEPTIDE | - |
dc.subject.keywordPlus | CONJUGATED POLYETHYLENIMINE | - |
dc.subject.keywordPlus | KAPPA-B | - |
dc.subject.keywordPlus | RECEPTOR | - |
dc.subject.keywordPlus | DELIVERY | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | HMGB1 | - |
dc.subject.keywordPlus | NEUROINFLAMMATION | - |
dc.identifier.url | https://pubs.rsc.org/en/content/articlelanding/2019/BM/C8BM01621F | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
222, Wangsimni-ro, Seongdong-gu, Seoul, 04763, Korea+82-2-2220-1365
COPYRIGHT © 2021 HANYANG UNIVERSITY.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.