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Journal of controlled release : official journal of the Controlled Release Society v.247, 2017년, pp.175 - 181   SCI SCIE
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A simple and highly effective catalytic nanozyme scavenger for organophosphorus neurotoxins

Efremenko, Elena N. (Chemistry Department, Lomonosov Moscow State University, 1 Lenin Hills, Building 3, Moscow 119991, Russia ); Lyagin, Ilya V. (Chemistry Department, Lomonosov Moscow State University, 1 Lenin Hills, Building 3, Moscow 119991, Russia ); Klyachko, Natalia L. (Chemistry Department, Lomonosov Moscow State University, 1 Lenin Hills, Building 3, Moscow 119991, Russia ); Bronich, Tatiana (Chemistry Department, Lomonosov Moscow State University, 1 Lenin Hills, Building 3, Moscow 119991, Russia ); Zavyalova, Natalia V. (27th Scientific Center of Ministry of Defense, 13 Brigadirsky Pereulok, Moscow 105005, Russia ); Jiang, Yuhang (Center for Nanotechnology in Drug Delivery, Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, 125 Mason Farm Road, Chapel Hill, NC 27599-7362, United States ); Kabanov, Alexander V. (Chemistry Department, Lomonosov Moscow State University, 1 Lenin Hills, Building 3, Moscow 119991, Russia );
  • 초록  

    Abstract A simple and highly efficient catalytic scavenger of poisonous organophosphorus compounds, based on organophosphorus hydrolase (OPH, EC 3.1.8.1), is produced in aqueous solution by electrostatic coupling of the hexahistidine tagged OPH (His 6 -OPH) and poly(ethylene glycol)- b -poly( L -glutamic acid) diblock copolymer. The resulting polyion complex, termed nano-OPH, has a spherical morphology and a diameter from 25nm to 100nm. Incorporation of His 6 -OPH in nano-OPH preserves catalytic activity and increases stability of the enzyme allowing its storage in aqueous solution for over a year. It also decreases the immune and inflammatory responses to His 6 -OPH in vivo as determined by anti-OPH IgG and cytokines formation in Sprague Dawley rats and Balb/c mice, respectively. The nano-OPH pharmacokinetic parameters are improved compared to the naked enzyme suggesting longer blood circulation after intravenous ( iv ) administrations in rats. Moreover, nano-OPH is bioavailable after intramuscular ( im ), intraperitoneal ( ip ) and even transbuccal ( tb ) administration, and has shown ability to protect animals from exposure to a pesticide, paraoxon and a warfare agent, VX. In particular, a complete protection against the lethal doses of paraoxon was observed with nano-OPH administered iv and ip as much as 17h, im 5.5h and tb 2h before the intoxication. Further evaluation of nano-OPH as a catalytic bioscavenger countermeasure against organophosphorus chemical warfare agents and pesticides is warranted. Graphical abstract [DISPLAY OMISSION]


  • 주제어

    Bioscavenger .   Nanoparticles .   Nanozyme .   Organophosphorus hydrolase .   Organophosphorus neurotoxin .   VX.  

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