Ribovski Laís, Joshi Bhagyashree, Gao Jie, Zuhorn Inge
Department of Biomedical Engineering, University Medical Center Groningen, University of Groningen, Groningen 9713 AV, the Netherlands.
Authors contributed equally.
Extracell Vesicles Circ Nucl Acids. 2023 Jun 30;4(2):283-305. doi: 10.20517/evcna.2023.26. eCollection 2023.
Extracellular vesicles (EVs) are natural micro-/nanoparticles that play an important role in intercellular communication. They are secreted by producer/donor cells and subsequent uptake by recipient/acceptor cells may result in phenotypic changes in these cells due to the delivery of cargo molecules, including lipids, RNA, and proteins. The process of endocytosis is widely described as the main mechanism responsible for cellular uptake of EVs, with endosomal escape of cargo molecules being a necessity for the functional delivery of EV cargo. Equivalent to synthetic micro-/nanoparticles, the properties of EVs, such as size and composition, together with environmental factors such as temperature, pH, and extracellular fluid composition, codetermine the interactions of EVs with cells, from binding to uptake, intracellular trafficking, and cargo release. Innovative assays for detection and quantification of the different steps in the EV formation and EV-mediated cargo delivery process have provided valuable insight into the biogenesis and cellular processing of EVs and their cargo, revealing the occurrence of EV recycling and degradation, next to functional cargo delivery, with the back fusion of the EV with the endosomal membrane standing out as a common cargo release pathway. In view of the significant potential for developing EVs as drug delivery systems, this review discusses the interaction of EVs with biological membranes en route to cargo delivery, highlighting the reported techniques for studying EV internalization and intracellular trafficking, EV-membrane fusion, endosomal permeabilization, and cargo delivery, including functional delivery of RNA cargo.
细胞外囊泡（EVs）是天然的微/纳米颗粒，在细胞间通讯中发挥着重要作用。它们由产生/供体细胞分泌，随后被受体/接受细胞摄取，由于脂质、RNA和蛋白质等货物分子的传递，可能导致这些细胞发生表型变化。内吞作用过程被广泛描述为细胞摄取EVs的主要机制，货物分子从内体逃逸是EV货物功能传递的必要条件。与合成微/纳米颗粒类似，EVs的性质，如大小和组成，以及温度、pH值和细胞外液组成等环境因素，共同决定了EVs与细胞的相互作用，从结合到摄取、细胞内运输和货物释放。用于检测和量化EV形成及EV介导的货物传递过程中不同步骤的创新检测方法，为深入了解EVs及其货物的生物发生和细胞处理提供了有价值的见解，揭示了除功能性货物传递外，EV回收和降解的发生情况，其中EV与内体膜的反向融合是一种常见的货物释放途径。鉴于将EVs开发为药物递送系统的巨大潜力，本综述讨论了EVs在货物递送过程中与生物膜的相互作用，重点介绍了用于研究EV内化和细胞内运输、EV-膜融合、内体通透化和货物递送（包括RNA货物的功能性递送）的报道技术。
