2.50
Hdl Handle:
http://hdl.handle.net/10033/621352
Title:
Engineering Extracellular Vesicles with the Tools of Enzyme Prodrug Therapy.
Authors:
Fuhrmann, Gregor; Chandrawati, Rona; Parmar, Paresh A; Keane, Timothy J; Maynard, Stephanie A; Bertazzo, Sergio; Stevens, Molly M
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.
Affiliation:
HIPS, Helmholtz-Institute für pharmazeutische Forschung Saarland, Universitätscampus E8.1, 66123 Saarbrücken, Germany.
Citation:
Engineering Extracellular Vesicles with the Tools of Enzyme Prodrug Therapy. 2018 Adv. Mater. Weinheim
Journal:
Advanced materials (Deerfield Beach, Fla.)
Issue Date:
23-Feb-2018
URI:
http://hdl.handle.net/10033/621352
DOI:
10.1002/adma.201706616
PubMed ID:
29473230
Type:
Article
Language:
en
ISSN:
1521-4095
Appears in Collections:
publications of the research group biogenic nanotherapeutics ([HIPS] BION)

Full metadata record

DC FieldValue Language
dc.contributor.authorFuhrmann, Gregoren
dc.contributor.authorChandrawati, Ronaen
dc.contributor.authorParmar, Paresh Aen
dc.contributor.authorKeane, Timothy Jen
dc.contributor.authorMaynard, Stephanie Aen
dc.contributor.authorBertazzo, Sergioen
dc.contributor.authorStevens, Molly Men
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.en
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

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