A simple and highly effective catalytic nanozyme scavenger for organophosphorus neurotoxins

Elena N. Efremenko, Ilya V. Lyagin, Natalia L. Klyachko, Tatiana Bronich, Natalia V. Zavyalova, Yuhang Jiang, Alexander V. Kabanov

Research output: Contribution to journalArticle

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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 25 nm to 100 nm. 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 17 h, im 5.5 h and tb 2 h before the intoxication. Further evaluation of nano-OPH as a catalytic bioscavenger countermeasure against organophosphorus chemical warfare agents and pesticides is warranted.

LanguageEnglish (US)
Pages175-181
Number of pages7
JournalJournal of Controlled Release
Volume247
DOIs
StatePublished - Feb 10 2017

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His-His-His-His-His-His
Neurotoxins
Paraoxon
Pesticides
Chemical Warfare Agents
Organophosphorus Compounds
Aryldialkylphosphatase
Enzyme Stability
Ethylene Glycol
Blood Circulation
Static Electricity
Intravenous Administration
Sprague Dawley Rats
Glutamic Acid
Pharmacokinetics
Cytokines
Enzymes

Keywords

  • Bioscavenger
  • Nanoparticles
  • Nanozyme
  • Organophosphorus hydrolase
  • Organophosphorus neurotoxin
  • VX

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Efremenko, E. N., Lyagin, I. V., Klyachko, N. L., Bronich, T., Zavyalova, N. V., Jiang, Y., & Kabanov, A. V. (2017). A simple and highly effective catalytic nanozyme scavenger for organophosphorus neurotoxins. Journal of Controlled Release, 247, 175-181. DOI: 10.1016/j.jconrel.2016.12.037

A simple and highly effective catalytic nanozyme scavenger for organophosphorus neurotoxins. / Efremenko, Elena N.; Lyagin, Ilya V.; Klyachko, Natalia L.; Bronich, Tatiana; Zavyalova, Natalia V.; Jiang, Yuhang; Kabanov, Alexander V.

In: Journal of Controlled Release, Vol. 247, 10.02.2017, p. 175-181.

Research output: Contribution to journalArticle

Efremenko, EN, Lyagin, IV, Klyachko, NL, Bronich, T, Zavyalova, NV, Jiang, Y & Kabanov, AV 2017, 'A simple and highly effective catalytic nanozyme scavenger for organophosphorus neurotoxins' Journal of Controlled Release, vol 247, pp. 175-181. DOI: 10.1016/j.jconrel.2016.12.037
Efremenko EN, Lyagin IV, Klyachko NL, Bronich T, Zavyalova NV, Jiang Y et al. A simple and highly effective catalytic nanozyme scavenger for organophosphorus neurotoxins. Journal of Controlled Release. 2017 Feb 10;247:175-181. Available from, DOI: 10.1016/j.jconrel.2016.12.037
Efremenko, Elena N. ; Lyagin, Ilya V. ; Klyachko, Natalia L. ; Bronich, Tatiana ; Zavyalova, Natalia V. ; Jiang, Yuhang ; Kabanov, Alexander V./ A simple and highly effective catalytic nanozyme scavenger for organophosphorus neurotoxins. In: Journal of Controlled Release. 2017 ; Vol. 247. pp. 175-181
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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 25 nm to 100 nm. 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 17 h, im 5.5 h and tb 2 h before the intoxication. Further evaluation of nano-OPH as a catalytic bioscavenger countermeasure against organophosphorus chemical warfare agents and pesticides is warranted.",
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