Microfluidic Production of Exosome-Mimicking Lipid Nanoparticles for Enhanced RNA Delivery: Role of Exosomal Proteins.

IF 8.3 2区材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY

ACS Applied Materials & Interfaces Pub Date : 2025-06-16 DOI:10.1021/acsami.5c06927

Masatoshi Maeki,Ayuka Niwa,Shota Oyama,Kyoko Aratani,Rina Ito,Yuichi Suzuki,Yusuke Sato,Akihiko Ishida,Hideyoshi Harashima,Manabu Tokeshi

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引用次数: 0

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.

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微流体生产的外泌体模拟脂质纳米颗粒增强RNA递送：外泌体蛋白的作用。

外泌体是细胞分泌的以脂质为基础的纳米颗粒，通过包裹和递送各种生物分子，如DNA、mRNA、miRNA和蛋白质，在细胞间通讯中起着至关重要的作用。基于它们跨越生物屏障、利用自然通讯机制和最小化免疫原性的能力，它们提供了作为药物递送系统（dds）的潜力。然而，外泌体的异质性成为功能分析和基于外泌体的dds开发的瓶颈。因此，需要工程技术来生产具有可控特性的外泌体或模仿外泌体的纳米颗粒，包括在其表面呈现特定的外泌体蛋白质。在这里，开发了一种一步微流控方法，用于生产用特定外泌体蛋白修饰的模拟外泌体的脂基纳米颗粒，从而能够控制所得到的外泌体的组成和特征。通过这种方法，制备了以四联蛋白（CD9、CD63、CD81）和整合素（ITG αVβ5、ITG α6β4）修饰的外泌体模拟纳米颗粒，这些纳米颗粒参与细胞信号转导和器官靶向。研究这些外泌体蛋白对RNA传递效率的影响发现，ITG α v β5修饰的模拟外泌体纳米颗粒在体外和体内都能显著增强RNA的传递。该研究为制备精确修饰的模拟外泌体纳米颗粒提供了一种方法，可用于阐明外泌体蛋白的功能和开发靶向dds。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Applied Materials & Interfaces 工程技术-材料科学：综合

CiteScore

16.00

自引率

6.30%

发文量

4978

审稿时长

1.8 months

期刊介绍： ACS Applied Materials & Interfaces is a leading interdisciplinary journal that brings together chemists, engineers, physicists, and biologists to explore the development and utilization of newly-discovered materials and interfacial processes for specific applications. Our journal has experienced remarkable growth since its establishment in 2009, both in terms of the number of articles published and the impact of the research showcased. We are proud to foster a truly global community, with the majority of published articles originating from outside the United States, reflecting the rapid growth of applied research worldwide.