Engineering Extracellular Vesicles with the Tools of Enzyme Prodrug Therapy

© 2018 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 30(2018), 15 vom: 01. Apr., Seite e1706616
1. Verfasser: Fuhrmann, Gregor (VerfasserIn)
Weitere Verfasser: Chandrawati, Rona, Parmar, Paresh A, Keane, Timothy J, Maynard, Stephanie A, Bertazzo, Sergio, Stevens, Molly M
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2018
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article enzyme prodrug therapy exosomes hydrogels microvesicles β-glucuronidase Drug Carriers Prodrugs
Beschreibung
Zusammenfassung:© 2018 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Extracellular vesicles (EVs) have recently gained significant attention as important mediators of intercellular communication, potential drug carriers, and disease biomarkers. These natural cell-derived nanoparticles are postulated to be biocompatible, stable under physiological conditions, and to show reduced immunogenicity as compared to other synthetic nanoparticles. Although initial clinical trials are ongoing, the use of EVs for therapeutic applications may be limited due to undesired off-target activity and potential "dilution effects" upon systemic administration which may affect their ability to reach their target tissues. To fully exploit their therapeutic potential, EVs are embedded into implantable biomaterials designed to achieve local delivery of therapeutics taking advantage of enzyme prodrug therapy (EPT). In this first application of EVs for an EPT approach, EVs are used as smart carriers for stabilizing enzymes in a hydrogel for local controlled conversion of benign prodrugs to active antiinflammatory compounds. It is shown that the natural EVs' antiinflammatory potential is comparable or superior to synthetic carriers, in particular upon repeated long-term incubations and in different macrophage models of inflammation. Moreover, density-dependent color scanning electron microscopy imaging of EVs in a hydrogel is presented herein, an impactful tool for further understanding EVs in biological settings
Beschreibung:Date Completed 28.01.2019
Date Revised 11.12.2024
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-4095
DOI:10.1002/adma.201706616