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Engineering Extracellular Vesicles with the Tools of Enzyme Prodrug Therapy

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 s... Full description

Journal Title: Advanced materials (Deerfield Beach Fla.), 2018, Vol.30(15), p.e1706616-e1706616
Main Author: Fuhrmann, Gregor
Other Authors: Chandrawati, Rona , Parmar, Paresh A , Keane, Timothy J , Maynard, Stephanie A , Bertazzo, Sergio , Stevens, Molly M
Format: Electronic Article Electronic Article
Language:
Subjects:
ID: ISSN: 0935-9648 ; E-ISSN: 1521-4095 ; DOI: 10.1002/adma.201706616 ; PMCID: 5901706 ; PMID: 29473230
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recordid: pubmed_central5901706
title: Engineering Extracellular Vesicles with the Tools of Enzyme Prodrug Therapy
format: Article
creator:
  • Fuhrmann, Gregor
  • Chandrawati, Rona
  • Parmar, Paresh A
  • Keane, Timothy J
  • Maynard, Stephanie A
  • Bertazzo, Sergio
  • Stevens, Molly M
subjects:
  • Article
  • -Glucuronidase
  • Enzyme Prodrug Therapy
  • Exosomes
  • Hydrogels
  • Microvesicles
ispartof: Advanced materials (Deerfield Beach, Fla.), 2018, Vol.30(15), p.e1706616-e1706616
description: 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.
language:
source:
identifier: ISSN: 0935-9648 ; E-ISSN: 1521-4095 ; DOI: 10.1002/adma.201706616 ; PMCID: 5901706 ; PMID: 29473230
fulltext: fulltext
issn:
  • 0935-9648
  • 09359648
  • 1521-4095
  • 15214095
url: Link


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titleEngineering Extracellular Vesicles with the Tools of Enzyme Prodrug Therapy
creatorFuhrmann, Gregor ; Chandrawati, Rona ; Parmar, Paresh A ; Keane, Timothy J ; Maynard, Stephanie A ; Bertazzo, Sergio ; Stevens, Molly M
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subjectArticle ; -Glucuronidase ; Enzyme Prodrug Therapy ; Exosomes ; Hydrogels ; Microvesicles
descriptionExtracellular 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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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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