細胞外小胞の電荷が機能を決める ―EV医薬品の品質評価に新指標―

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2026-05-14 東京大学

東京大学大学院工学系研究科の研究グループは、細胞外小胞(EV)の表面電荷と膜脂質組成の関係を体系的に整理し、EV機能を規定する重要因子であることを明らかにした。EVは細胞間情報伝達を担うナノ粒子で、診断や医薬品応用への期待が高まる一方、品質評価基準の未整備が課題だった。研究では、エクソソームが比較的弱い負電荷を示す一方、細胞膜由来EVは強い負電荷を持つ理由を、リン脂質ホスファチジルセリン(PS)の膜内外分布による「膜脂質非対称性」から説明した。さらに、表面電荷(ゼータ電位)が細胞状態やEV種類に応じて変化し、生理状態や機能を反映する有力な品質指標となる可能性を示した。これにより、EV医薬品の分類・分離・規格化に向けた基盤構築が期待されるほか、表面電荷制御による標的指向性向上や体内動態最適化など、次世代ナノ医療技術開発への応用も見込まれる。

細胞外小胞の電荷が機能を決める ―EV医薬品の品質評価に新指標―
細胞外小胞の膜脂質構造と表面電荷の違い

<関連情報>

細胞外小胞の機能の根底にある負の表面電荷と膜脂質組成 Negative Surface Charge and Membrane Lipid Composition Underlying Extracellular Vesicle Function

Naohiro Seo,and Takanori Ichiki
ACS Nano Medicine  Published: March 11, 2026
DOI:https://doi.org/10.1021/acsnanomed.5c00108

Abstract

Exosomes (EXOs), originating from multivesicular late endosomes and plasma-membrane-derived extracellular vesicles (PM-EVs), termed microvesicles, ectosomes, oncosomes, and apoptotic bodies, adopt a spherical shape with a lipid bilayer membrane and are released from various cells. EXOs play key roles in intercellular communication and physiological regulation. PM-EVs reflect cellular activation states and are involved in coagulation and inflammation. Both types of EVs possess an anionic surface charge resulting from scramblase-mediated translocation or nonenzymatic scrambling of phosphatidylserine (PS) from the inner to the outer leaflet of the lipid bilayer, as observed in the membranes of dead cells. In addition, glycosphingolipids (GSLs) and glycoproteins containing sialic acid and phosphatidylinositol and its phosphorylated derivatives contribute to the negative charge on the EV surface. Anion-exchange column chromatography has shown that the surface of EXOs exhibits a weaker negative charge than that of other PM-EVs from the plasma membrane, correlating with the magnitude of the negative ζ-potential value. Furthermore, fluctuations in the ζ-potential values of EVs can be used to predict the biological and physiological states of the source cells. The PS proportion in the total membrane lipids of EVs is nearly equivalent between EXOs and other PM-EVs, suggesting that EXOs maintain membrane lipid asymmetry to some extent, similar to the plasma membrane of living cells, although the underlying mechanism remains unknown.

有機化学・薬学
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