Detoxification of Organophosphate Poisoning Using Nanoparticle Bioscavengers.

Abstract

Organophosphate poisoning is highly lethal as organophosphates, which are commonly found in insecticides and nerve agents, cause irreversible phosphorylation and inactivation of acetylcholinesterase (AChE), leading to neuromuscular disorders via accumulation of acetylcholine in the body. Direct interception of organophosphates in the systemic circulation thus provides a desirable strategy in treatment of the condition. Inspired by the presence of AChE on red blood cell (RBC) membranes, we explored a biomimetic nanoparticle consisting of a polymeric core surrounded by RBC membranes to serve as an anti-organophosphate agent. Through in vitro studies, we demonstrated that the biomimetic nanoparticles retain the enzymatic activity of membrane-bound AChE and are able to bind to a model organophosphate, dichlorvos, precluding its inhibitory effect on other enzymatic substrates. In a mouse model of organophosphate poisoning, the nanoparticles were shown to improve the AChE activity in the blood and markedly improved the survival of dichlorvos-challenged mice.

• Authors: Zhiqing Pang, Che-Ming J Hu, Ronnie H Fang, Brian T Luk, Weiwei Gao, Fei Wang, Erdembileg Chuluun, Pavimol Angsantikul, Soracha Thamphiwatana, Weiyue Lu, Xinguo Jiang, Liangfang Zhang
• Journal: ACS nano (ACS Nano) Vol. 9 Issue 6 Pg. 6450-8 (Jun 23 2015) ISSN: 1936-086X [Electronic] United States
• PMID: 26053868 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Dichlorvos
• Acetylcholinesterase

Topics

• Acetylcholinesterase (metabolism)
• Animals
• Biomimetic Materials (chemistry, pharmacology)
• Dichlorvos (administration & dosage, antagonists & inhibitors, toxicity)
• Disease Models, Animal
• Erythrocytes (drug effects, metabolism)
• Male
• Mice
• Mice, Inbred Strains
• Nanoparticles (chemistry)
• Organophosphate Poisoning (drug therapy)