Interleukin-4-carrying small extracellular vesicles with a high potential as anti-inflammatory therapeutics based on modulation of macrophage function


Posted: 2021-10-15 19:00:00
Biomaterials . 2021 Oct 9;278:121160. doi: 10.1016/j.biomaterials.2021.121160. Online ahead of print. Affiliations Expand Affiliations 1 Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshidashimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan. 2 Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshidashimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan. Electronic address: ytakahashi@pharm.kyoto-u.ac.jp. Item in Clipboard Misako Takenaka et al. Biomaterials. 2021. Show details Display options Display options Format Biomaterials . 2021 Oct 9;278:121160. doi: 10.1016/j.biomaterials.2021.121160. Online ahead of print. Affiliations 1 Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshidashimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan. 2 Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshidashimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan. Electronic address: ytakahashi@pharm.kyoto-u.ac.jp. Item in Clipboard CiteDisplay options Display options Format Abstract Interleukin-4 (IL4), a Th2-type cytokine that can drive M2 macrophage polarization, is expected to be used as an anti-inflammatory therapy agent as M2 polarization of macrophages can ameliorate chronic inflammation. However, several problems, such as the low effectiveness and side effects, have hampered the clinical application. To safely and effectively use IL4, an efficient delivery of IL4 to target cells, macrophages, is necessary. Small extracellular vesicles (sEVs) are promising candidates as macrophage delivery carriers because they are efficiently recognized by macrophages. In addition, considering the property of IL4 signaling, for which the internalization of IL4 receptor into the cellular compartment is important, and sEV uptake mechanism by macrophages, sEVs are expected to amplify IL4 signaling. In this study, we developed IL4-carrying sEVs (IL4-sEVs) by genetically engineering sEV-producing cells. We investigated the bioactivity of IL4-sEVs using RAW264.7 macrophages and their potential for therapeutic application to the treatment of an inflammatory disease using collagen-induced arthritis model mice. IL4-sEVs exhibited stronger anti-inflammatory effects on M1-polarized macrophages through M2 polarization of macrophages than those of soluble IL4 proteins. Moreover, IL4-sEVs exhibited more effective therapeutic effects on rheumatoid arthritis than those of IL4. These results indicate that IL4-carrying sEVs are promising anti-inflammatory therapeutics. Keywords: Anti-inflammatory therapy; Drug delivery; Interleukin-4; Macrophage regulation; Small extracellular vesicles. Copyright © 2021 Elsevier Ltd. All rights reserved. [x] Cite Copy Format: Send To [x]

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バイオクイックニュース日本語版:エクソソーム特集

バイオクイックニュース日本語版
8月 01, 2016 バイオアソシエイツ

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オランダのロッテルダムで2016年5月4日から7日までの4日間開催された国際細胞外小胞学会総会 (ISEV 2016) の最終日土曜日は半日の閉会会議で、興味深い新しい研究や4日間の会期中に発表されたいくつかの優れた研究の授賞式などが行われた。 総会はJan Lotvall前会長が、オーストラリアのLa Trobe University, Department of Biochemistry & Geneticsの学部長を務めるAndy Hill氏 (写真) に会長職を引き渡す挨拶を行い、ISEV…

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