TY - JOUR
T1 - A simple and highly effective catalytic nanozyme scavenger for organophosphorus neurotoxins
AU - Efremenko, Elena N.
AU - Lyagin, Ilya V.
AU - Klyachko, Natalia L.
AU - Bronich, Tatiana
AU - Zavyalova, Natalia V.
AU - Jiang, Yuhang
AU - Kabanov, Alexander V.
N1 - Funding Information:
This work was funded by the Ministry of Education and Science of the Russian Federation (contract No. 11.G34.31.004 to A.V.K.). The testing of the VX was carried out under the research agreement between the Faculty of Chemistry of MSU and the 27th Scientific Center of Ministry of Defense in the institute's facility. We thank research fellows of the 27th Scientific Center of Ministry of Defense for technical assistance in animal experiments and Natalia Nukolova (MSU) for carrying out the MTT assay.
Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/2/10
Y1 - 2017/2/10
N2 - 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.
AB - 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.
KW - Bioscavenger
KW - Nanoparticles
KW - Nanozyme
KW - Organophosphorus hydrolase
KW - Organophosphorus neurotoxin
KW - VX
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U2 - 10.1016/j.jconrel.2016.12.037
DO - 10.1016/j.jconrel.2016.12.037
M3 - Article
C2 - 28043864
AN - SCOPUS:85009084409
VL - 247
SP - 175
EP - 181
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
ER -