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Engineered nanoparticles bind elapid snake venom toxins and inhibit venom-induced dermonecrosis

Envenomings by snakebites constitute a serious and challenging global health issue. The mainstay in the therapy of snakebite envenomings is the parenteral administration of animal-derived antivenoms. Significantly, antivenoms are only partially effective in the control of local tissue damage. A nove...

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Autores principales: O’Brien, Jeffrey, Lee, Shih-Hui, Gutiérrez, José María, Shea, Kenneth J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171825/
https://www.ncbi.nlm.nih.gov/pubmed/30286075
http://dx.doi.org/10.1371/journal.pntd.0006736
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author O’Brien, Jeffrey
Lee, Shih-Hui
Gutiérrez, José María
Shea, Kenneth J.
author_facet O’Brien, Jeffrey
Lee, Shih-Hui
Gutiérrez, José María
Shea, Kenneth J.
author_sort O’Brien, Jeffrey
collection PubMed
description Envenomings by snakebites constitute a serious and challenging global health issue. The mainstay in the therapy of snakebite envenomings is the parenteral administration of animal-derived antivenoms. Significantly, antivenoms are only partially effective in the control of local tissue damage. A novel approach to mitigate the progression of local tissue damage that could complement the antivenom therapy of envenomings is proposed. We describe an abiotic hydrogel nanoparticle engineered to bind to and modulate the activity of a diverse array of PLA(2) and 3FTX isoforms found in Elapidae snake venoms. These two families of protein toxins share features that are associated with their common (membrane) targets, allowing for nanoparticle sequestration by a mechanism that differs from immunological (epitope) selection. The nanoparticles are non-toxic in mice and inhibit dose-dependently the dermonecrotic activity of Naja nigricollis venom.
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spelling pubmed-61718252018-10-19 Engineered nanoparticles bind elapid snake venom toxins and inhibit venom-induced dermonecrosis O’Brien, Jeffrey Lee, Shih-Hui Gutiérrez, José María Shea, Kenneth J. PLoS Negl Trop Dis Research Article Envenomings by snakebites constitute a serious and challenging global health issue. The mainstay in the therapy of snakebite envenomings is the parenteral administration of animal-derived antivenoms. Significantly, antivenoms are only partially effective in the control of local tissue damage. A novel approach to mitigate the progression of local tissue damage that could complement the antivenom therapy of envenomings is proposed. We describe an abiotic hydrogel nanoparticle engineered to bind to and modulate the activity of a diverse array of PLA(2) and 3FTX isoforms found in Elapidae snake venoms. These two families of protein toxins share features that are associated with their common (membrane) targets, allowing for nanoparticle sequestration by a mechanism that differs from immunological (epitope) selection. The nanoparticles are non-toxic in mice and inhibit dose-dependently the dermonecrotic activity of Naja nigricollis venom. Public Library of Science 2018-10-04 /pmc/articles/PMC6171825/ /pubmed/30286075 http://dx.doi.org/10.1371/journal.pntd.0006736 Text en © 2018 O’Brien et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
O’Brien, Jeffrey
Lee, Shih-Hui
Gutiérrez, José María
Shea, Kenneth J.
Engineered nanoparticles bind elapid snake venom toxins and inhibit venom-induced dermonecrosis
title Engineered nanoparticles bind elapid snake venom toxins and inhibit venom-induced dermonecrosis
title_full Engineered nanoparticles bind elapid snake venom toxins and inhibit venom-induced dermonecrosis
title_fullStr Engineered nanoparticles bind elapid snake venom toxins and inhibit venom-induced dermonecrosis
title_full_unstemmed Engineered nanoparticles bind elapid snake venom toxins and inhibit venom-induced dermonecrosis
title_short Engineered nanoparticles bind elapid snake venom toxins and inhibit venom-induced dermonecrosis
title_sort engineered nanoparticles bind elapid snake venom toxins and inhibit venom-induced dermonecrosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171825/
https://www.ncbi.nlm.nih.gov/pubmed/30286075
http://dx.doi.org/10.1371/journal.pntd.0006736
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