title: A simple and highly effective catalytic nanozyme scavenger for organophosphorus neurotoxins.
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 (His6-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 His6-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 His6-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.
authors.affiliation: Chemistry Department, Lomonosov Moscow State University, 1 Lenin Hills, Building 3, Moscow 119991, Russia. Electronic address: elena_efremenko@list.ru.
authors.forename: Elena N
authors.initials: EN
authors.lastname: Efremenko
authors.affiliation: Chemistry Department, Lomonosov Moscow State University, 1 Lenin Hills, Building 3, Moscow 119991, Russia.
authors.forename: Ilya V
authors.initials: IV
authors.lastname: Lyagin
authors.affiliation: Chemistry Department, Lomonosov Moscow State University, 1 Lenin Hills, Building 3, Moscow 119991, Russia; 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.
authors.forename: Natalia L
authors.initials: NL
authors.lastname: Klyachko
authors.affiliation: Chemistry Department, Lomonosov Moscow State University, 1 Lenin Hills, Building 3, Moscow 119991, Russia; Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, S 42nd St. & Emile St., Omaha, NE 68198, United States.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Bronich
authors.affiliation: 27th Scientific Center of Ministry of Defense, 13 Brigadirsky Pereulok, Moscow 105005, Russia.
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Zavyalova
authors.affiliation: 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.
authors.forename: Yuhang
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Chemistry Department, Lomonosov Moscow State University, 1 Lenin Hills, Building 3, Moscow 119991, Russia; 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; Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, S 42nd St. & Emile St., Omaha, NE 68198, United States. Electronic address: kabanov@unc.edu.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Kabanov
mesh_terms: D000818:Animals; D043303:Aryldialkylphosphatase / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D007306:Insecticides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008297:Male; D008807:Mice, Inbred BALB C; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D062025:Organophosphate Poisoning / Q000517:prevention & control*; D009943:Organophosphorus Compounds / Q000037:antagonists & inhibitors / Q000633:toxicity; D010261:Paraoxon / Q000037:antagonists & inhibitors / Q000633:toxicity*; D017207:Rats, Sprague-Dawley
chemical_list: D007306:Insecticides; D009498:Neurotoxins; D009943:Organophosphorus Compounds; D043303:Aryldialkylphosphatase; D010261:Paraoxon
keywords: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (PubChem CID: 64965); 5,5′-dithiobis(2-nitrobenzoic acid) (PubChem CID: 6254); Acetylthiocholine chloride (PubChem CID: 22411); Bioscavenger; Nanoparticles; Nanozyme; Organophosphorus hydrolase; Organophosphorus neurotoxin; Paraoxon (PubChem CID: 9395); Parathion (PubChem CID: 991); Parathion-methyl (PubChem CID: 4130); VX; VX (PubChem CID: 39793)