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Engineering Extracellular Vesicles with the Tools of Enzyme Prodrug Therapy.

Fuhrmann, G; Chandrawati, R; Parmar, PA; Keane, TJ; Maynard, SA; Bertazzo, S; Stevens, MM; (2018) Engineering Extracellular Vesicles with the Tools of Enzyme Prodrug Therapy. Advanced Materials , 30 (15) , Article 1706616. 10.1002/adma.201706616. Green open access

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Abstract

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.

Type: Article
Title: Engineering Extracellular Vesicles with the Tools of Enzyme Prodrug Therapy.
Location: Germany
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/adma.201706616
Publisher version: http://dx.doi.org/10.1002/adma.201706616
Language: English
Additional information: Copyright © 2018 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: Enzyme prodrug therapy, exosomes, hydrogels, microvesicles, β-glucuronidase
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Med Phys and Biomedical Eng
URI: https://discovery.ucl.ac.uk/id/eprint/10044526
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