A simple and highly effective catalytic nanozyme scavenger for organophosphorus neurotoxins

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• 作者：Elena N. Efremenko^a ; ^{elena_efremenko@list.ru} ; Ilya V. Lyagin^a ; Natalia L. Klyachko^a ; ^b ; Tatiana Bronich^a ; ^c ; Natalia V. Zavyalova^d ; Yuhang Jiang^b ; Alexander V. Kabanov^a ; ^b ; ^c ; ^{kabanov@unc.edu}
• 关键词：Acetylthiocholine chloride (PubChem CID ; 22411) ; 5 ; 5&prime ; -dithiobis(2-nitrobenzoic acid) (PubChem CID ; 6254) ; 3-(4 ; 5-dimethylthiazol-2-yl)-2 ; 5-diphenyltetrazolium bromide (PubChem CID ; 64965) ; Paraoxon (PubChem CID ; 9395) ; Parathion (PubChem CID ; 991) ; Parathion-methyl (PubChem CID ; 4130) ; VX (PubChem CID ; 39793)
• 刊名：Journal of Controlled Release
• 出版年：2017
• 出版时间：10 February 2017
• 年：2017
• 卷：247
• 期：Complete
• 页码：175-181
• 全文大小：652 K
• 卷排序：247

文摘

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.