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Biocompatible polymeric nanocomplexes as an intracellular stimuli-sensitive prodrug for type-2 diabetes combination therapy
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Wang, Feng-Zhen | - |
dc.contributor.author | Xie, Zhi-Shen | - |
dc.contributor.author | Xing, Lei | - |
dc.contributor.author | Zhang, Bing-Feng | - |
dc.contributor.author | Zhang, Jia-Liang | - |
dc.contributor.author | Cui, Peng-Fei | - |
dc.contributor.author | Qiao, Jan-Bin | - |
dc.contributor.author | Shi, Kun | - |
dc.contributor.author | Cho, Chong-Su | - |
dc.contributor.author | Cho, Myung-Haing | - |
dc.contributor.author | Xu, Xiaojun | - |
dc.contributor.author | Li, Ping | - |
dc.contributor.author | Jiang, Hu-Lin | - |
dc.date.accessioned | 2021-01-31T08:40:36Z | - |
dc.date.available | 2021-01-31T08:40:36Z | - |
dc.date.created | 2018-01-10 | - |
dc.date.issued | 2015-12 | - |
dc.identifier.citation | Biomaterials, Vol.73, pp.149-159 | - |
dc.identifier.issn | 0142-9612 | - |
dc.identifier.other | 10810 | - |
dc.identifier.uri | https://hdl.handle.net/10371/172344 | - |
dc.description.abstract | Combination therapy is usually considered as a promising strategy owing to its advantages such as reduced doses, minimized side effects and improved therapeutic efficiency in a variety of diseases including diabetes. Here we synthesized a new highly intracellular stimuli-sensitive chitosan-graft-metformin (CS-MET) prodrug by imine reaction between oxidative chitosan and metformin for type 2 diabetes (T2D) therapy. Hypothetically, CS-MET functions dually as an anti-diabetes prodrug as well as a gene delivery vector without superfluous materials. CS-MET formed nanocomplexes with therapeutic gene through electrostatic interactions and entered cells by Organic Cation Transporter (OCT)-independent endocytosis. The incorporation of metformin into chitosan has been found to increase endosomal escape via the proton sponge effect. When vector carrying a short-hairpin RNA (shRNA) silencing sterol regulatory element-binding protein (SREBP), a major transcription factor involved in de novo lipogenisis, it reduced the SREBP mRNA and proteins efficiently. Furthermore, by intraperitoneal injection, CS-MET/shSREBP nanocomplexes effectively knocked down SREBP in livers of western-type diet (WD)-induced obese C57BL/6J mice, markedly reversed insulin resistance and alleviated the fatty liver phenotype without obvious toxic effects. Thus we were able to show that the intracellular stimuli-sensitive CS-MET prodrug renders a potential platform to increase the anti-diabetes activity with synergistic enhancement of gene therapy. (C) 2015 Elsevier Ltd. All rights reserved. | - |
dc.language | 영어 | - |
dc.publisher | Pergamon Press Ltd. | - |
dc.title | Biocompatible polymeric nanocomplexes as an intracellular stimuli-sensitive prodrug for type-2 diabetes combination therapy | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 조명행 | - |
dc.identifier.doi | 10.1016/j.biomaterials.2015.09.013 | - |
dc.citation.journaltitle | Biomaterials | - |
dc.identifier.wosid | 000363830200015 | - |
dc.identifier.scopusid | 2-s2.0-84943561309 | - |
dc.citation.endpage | 159 | - |
dc.citation.startpage | 149 | - |
dc.citation.volume | 73 | - |
dc.identifier.sci | 000363830200015 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Cho, Myung-Haing | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | ORGANIC CATION TRANSPORTER | - |
dc.subject.keywordPlus | INSULIN-RESISTANCE | - |
dc.subject.keywordPlus | GENETIC-VARIATION | - |
dc.subject.keywordPlus | METFORMIN ACTION | - |
dc.subject.keywordPlus | SREBP ACTIVITY | - |
dc.subject.keywordPlus | CELL-GROWTH | - |
dc.subject.keywordPlus | DELIVERY | - |
dc.subject.keywordPlus | CHITOSAN | - |
dc.subject.keywordPlus | MICE | - |
dc.subject.keywordPlus | CARRIER | - |
dc.subject.keywordAuthor | Combination therapy | - |
dc.subject.keywordAuthor | Diabetes | - |
dc.subject.keywordAuthor | Prodrug | - |
dc.subject.keywordAuthor | Stimuli-sensitive | - |
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