エクソソーム模倣ナノ粒子の作製に成功~エクソソーム創薬や診断技術の確立に期待~

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2025-06-19 北海道大学

北海道大学の真栄城正寿准教授らは、マイクロ流体デバイスを用い、エクソソームを模倣した脂質ナノ粒子の作製に成功しました。粒径や表面タンパク質(CD9、CD63、CD81、インテグリンなど)を均一に制御し、siRNAやmRNAも高効率で内包可能。実験では、インテグリン(特にITGαVβ5)を提示した粒子がRNA送達効率を細胞や肝臓で大きく向上させることを確認。本成果は、エクソソーム機能解明、次世代DDS、診断技術への応用が期待される。

エクソソーム模倣ナノ粒子の作製に成功~エクソソーム創薬や診断技術の確立に期待~
本研究の概要図:エクソソーム模倣ナノ粒子の作製方法の概略図

<関連情報>

マイクロ流体デバイスを用いたエクソソーム模倣脂質ナノ粒子の作製:エクソソームタンパク質の役割の解明 Microfluidic Production of Exosome-Mimicking Lipid Nanoparticles for Enhanced RNA Delivery: Role of Exosomal Proteins

Masatoshi Maeki,Ayuka Niwa,Shota Oyama,Kyoko Aratani,Rina Ito,Yuichi Suzuki,Yusuke Sato,Akihiko Ishida,Hideyoshi Harashima,and Manabu Tokeshi
ACS Applied Materials & Interfaces  Published: June 16, 2025
DOI:https://doi.org/10.1021/acsami.5c06927

Abstract

Exosomes, which are cell-secreted lipid-based nanoparticles, play a crucial role in intercellular communication by encapsulating and delivering various biomolecules such as DNA, mRNA, miRNA, and proteins. They offer potential as drug delivery systems (DDSs) based on their ability to cross biological barriers, use natural communication mechanisms, and minimize immunogenicity. However, the heterogeneity of exosomes presents a bottleneck for functional analysis and the development of exosome-based DDSs. Therefore, engineering techniques are needed to produce exosomes or exosome-mimicking nanoparticles with controlled characteristics, including the presentation of specific exosomal proteins on their surface. Here, a one-step microfluidic method for producing exosome-mimicking lipid-based nanoparticles decorated with specific exosomal proteins was developed, enabling control over the composition and characteristics of the resulting exosomes. Exosome-mimicking nanoparticles decorated with tetraspanin proteins (CD9, CD63, CD81) and integrins (ITG αVβ5, ITG α6β4), which are involved in cell signaling and organ targeting, were thereby generated. Investigating the impact of these exosomal proteins on RNA delivery efficiency revealed that ITG αVβ5-decorated exosome-mimicking nanoparticles significantly enhance RNA delivery both in vitro and in vivo. This study provides an approach for producing precisely decorated exosome-mimicking nanoparticles, which may be applied to elucidate the functions of exosomal proteins and develop targeted DDSs.

有機化学・薬学
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