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Nanoscavenger provides long-term prophylactic protection against nerve agents in rodents.
Zhang, Peng; Liu, Erik J; Tsao, Caroline; Kasten, Shane A; Boeri, Michael V; Dao, Thuy L; DeBus, Sandra J; Cadieux, C Linn; Baker, Cetara A; Otto, Tamara C; Cerasoli, Douglas M; Chen, Yantao; Jain, Priyesh; Sun, Fang; Li, Wenchen; Hung, Hsiang-Chieh; Yuan, Zhefan; Ma, Jinrong; Bigley, Andrew N; Raushel, Frank M; Jiang, Shaoyi.
Affiliation
  • Zhang P; Department of Chemical Engineering, University of Washington, 3781 Okanogan Lane NE, Box 351750, Seattle, WA 98195, USA.
  • Liu EJ; Department of Chemical Engineering, University of Washington, 3781 Okanogan Lane NE, Box 351750, Seattle, WA 98195, USA.
  • Tsao C; Department of Chemical Engineering, University of Washington, 3781 Okanogan Lane NE, Box 351750, Seattle, WA 98195, USA.
  • Kasten SA; Physiology and Immunology Branch, Research Division, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010, USA.
  • Boeri MV; Physiology and Immunology Branch, Research Division, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010, USA.
  • Dao TL; Physiology and Immunology Branch, Research Division, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010, USA.
  • DeBus SJ; Physiology and Immunology Branch, Research Division, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010, USA.
  • Cadieux CL; Physiology and Immunology Branch, Research Division, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010, USA.
  • Baker CA; Physiology and Immunology Branch, Research Division, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010, USA.
  • Otto TC; Physiology and Immunology Branch, Research Division, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010, USA.
  • Cerasoli DM; Physiology and Immunology Branch, Research Division, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010, USA.
  • Chen Y; Department of Chemical Engineering, University of Washington, 3781 Okanogan Lane NE, Box 351750, Seattle, WA 98195, USA.
  • Jain P; Department of Chemical Engineering, University of Washington, 3781 Okanogan Lane NE, Box 351750, Seattle, WA 98195, USA.
  • Sun F; Department of Chemical Engineering, University of Washington, 3781 Okanogan Lane NE, Box 351750, Seattle, WA 98195, USA.
  • Li W; Department of Chemical Engineering, University of Washington, 3781 Okanogan Lane NE, Box 351750, Seattle, WA 98195, USA.
  • Hung HC; Department of Chemical Engineering, University of Washington, 3781 Okanogan Lane NE, Box 351750, Seattle, WA 98195, USA.
  • Yuan Z; Department of Chemical Engineering, University of Washington, 3781 Okanogan Lane NE, Box 351750, Seattle, WA 98195, USA.
  • Ma J; Department of Chemical Engineering, University of Washington, 3781 Okanogan Lane NE, Box 351750, Seattle, WA 98195, USA.
  • Bigley AN; Department of Chemistry, Texas A&M University, College Station, TX 77842, USA.
  • Raushel FM; Department of Chemistry, Texas A&M University, College Station, TX 77842, USA.
  • Jiang S; Department of Chemical Engineering, University of Washington, 3781 Okanogan Lane NE, Box 351750, Seattle, WA 98195, USA. sjiang@uw.edu.
Sci Transl Med ; 11(473)2019 01 02.
Article in En | MEDLINE | ID: mdl-30602537
ABSTRACT
Nerve agents are a class of organophosphorus compounds (OPs) that blocks communication between nerves and organs. Because of their acute neurotoxicity, it is extremely difficult to rescue the victims after exposure. Numerous efforts have been devoted to search for an effective prophylactic nerve agent bioscavenger to prevent the deleterious effects of these compounds. However, low scavenging efficiency, unfavorable pharmacokinetics, and immunological problems have hampered the development of effective drugs. Here, we report the development and testing of a nanoparticle-based nerve agent bioscavenger (nanoscavenger) that showed long-term protection against OP intoxication in rodents. The nanoscavenger, which catalytically breaks down toxic OP compounds, showed a good pharmacokinetic profile and negligible immune response in a rat model of OP intoxication. In vivo administration of the nanoscavenger before or after OP exposure in animal models demonstrated protective and therapeutic efficacy. In a guinea pig model, a single prophylactic administration of the nanoscavenger effectively prevented lethality after multiple sarin exposures over a 1-week period. Our results suggest that the prophylactic administration of the nanoscavenger might be effective in preventing the toxic effects of OP exposure in humans.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Protective Agents / Nanoparticles / Nerve Agents Type of study: Prognostic_studies Limits: Animals Language: En Journal: Sci Transl Med Journal subject: CIENCIA / MEDICINA Year: 2019 Document type: Article Affiliation country:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Protective Agents / Nanoparticles / Nerve Agents Type of study: Prognostic_studies Limits: Animals Language: En Journal: Sci Transl Med Journal subject: CIENCIA / MEDICINA Year: 2019 Document type: Article Affiliation country: