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      Exploring interactions between extracellular vesicles and cells for innovative drug delivery system design.

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          Abstract

          Extracellular vesicles (EVs) are submicron cell-secreted structures containing proteins, nucleic acids and lipids. EVs can functionally transfer these cargoes from one cell to another to modulate physiological and pathological processes. Due to their presumed biocompatibility and capacity to circumvent canonical delivery barriers encountered by synthetic drug delivery systems, EVs have attracted considerable interest as drug delivery vehicles. However, it is unclear which mechanisms and molecules orchestrate EV-mediated cargo delivery to recipient cells. Here, we review how EV properties have been exploited to improve the efficacy of small molecule drugs. Furthermore, we explore which EV surface molecules could be directly or indirectly involved in EV-mediated cargo transfer to recipient cells and discuss the cellular reporter systems with which such transfer can be studied. Finally, we elaborate on currently identified cellular processes involved in EV cargo delivery. Through these topics, we provide insights in critical effectors in the EV-cell interface which may be exploited in nature-inspired drug delivery strategies.

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          Author and article information

          Journal
          Adv Drug Deliv Rev
          Advanced drug delivery reviews
          Elsevier BV
          1872-8294
          0169-409X
          June 2021
          : 173
          Affiliations
          [1 ] CDL Research, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands. Electronic address: s.kooijmans-2@umcutrecht.nl.
          [2 ] CDL Research, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, the Netherlands. Electronic address: o.g.dejong@uu.nl.
          [3 ] CDL Research, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands. Electronic address: r.schiffelers@umcutrecht.nl.
          Article
          S0169-409X(21)00095-8
          10.1016/j.addr.2021.03.017
          33798644
          593f8b4f-1f87-4a8a-aff4-718b4bd2299f
          History

          Exosomes,Small molecules,Reporter systems,RNA delivery,Protein delivery,Extracellular vesicles,Extracellular vesicle surface,Drug delivery,Uptake mechanisms

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