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dc.contributor.authorFuhrmann, Gregor
dc.contributor.authorChandrawati, Rona
dc.contributor.authorParmar, Paresh A
dc.contributor.authorKeane, Timothy J
dc.contributor.authorMaynard, Stephanie A
dc.contributor.authorBertazzo, Sergio
dc.contributor.authorStevens, Molly M
dc.date.accessioned2018-04-13T08:27:37Z
dc.date.available2018-04-13T08:27:37Z
dc.date.issued2018-02-23
dc.identifier.citationEngineering Extracellular Vesicles with the Tools of Enzyme Prodrug Therapy. 2018 Adv. Mater. Weinheimen
dc.identifier.issn1521-4095
dc.identifier.pmid29473230
dc.identifier.doi10.1002/adma.201706616
dc.identifier.urihttp://hdl.handle.net/10033/621352
dc.description.abstractExtracellular 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.
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleEngineering Extracellular Vesicles with the Tools of Enzyme Prodrug Therapy.en
dc.typeArticleen
dc.contributor.departmentHIPS, Helmholtz-Institute für pharmazeutische Forschung Saarland, Universitätscampus E8.1, 66123 Saarbrücken, Germany.en
dc.identifier.journalAdvanced materials (Deerfield Beach, Fla.)en
refterms.dateFOA2018-06-13T03:41:15Z
html.description.abstractExtracellular 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.


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