Extracellular Vesicles Mediate the Intercellular Exchange of Nanoparticles. Issue 7 (17th January 2022)

• Record Type: Journal Article
• Authors: Wu, Xian; Tang, Tang; Wei, Yushuang; Cummins, Katherine A.; Wood, David K.; Pang, Hong‐Bo
• Is Part Of: Advanced science. Volume 9:Issue 7(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-01-17
• Subjects: 3D assay -- extracellular vesicles -- intercellular exchange -- nanoparticle transport; Science -- Periodicals; 505
• DOI: 10.1002/advs.202102441
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: To exert their therapeutic effects, nanoparticles (NPs) often need to travel into the tissues composed of multilayered cells. Accumulative evidence has revealed the crucial role of transcellular transport route (entry into one cell, exocytosis, and re‐entry into another) in this process. While NP endocytosis and subcellular transport are intensively characterized, the exocytosis and re‐entry steps are poorly understood, which becomes a barrier for NP delivery into complex tissues. Here, the authors term the exocytosis and re‐entry steps together as intercellular exchange. A collagen‐based three‐dimension assay is developed to specifically quantify the intercellular exchange of NPs, and distinguish the contributions of several potential mechanisms. The authors show that NPs can be exocytosed freely or enclosed inside extracellular vesicles (EVs) for re‐entry, while direct cell–cell contact is hardly involved. EVs account for a significant fraction of NP intercellular exchange, and its importance in NP transport is demonstrated in vitro and in vivo. While freely released NPs engage with the same receptors for re‐entry, EV‐enclosed ones bypass this dependence. These studies provide an easy and precise system to investigate the intercellular exchange stage of NP delivery, and shed the first light in the importance of EVs in NP transport between cells and into complex tissues. Abstract : A 3D assay is developed to exclusively quantify the intercellular exchange of nanoparticles (NPs) in vitro. The results demonstrate that peptide‐functionalized NPs, after engulfed by one cell, can be secreted inside extracellular vesicle (EVs) for re‐entry into neighboring cells. EV biogenesis is proven important in vitro and in vivo for intercellular exchange and tissue penetration of NPs.