title: 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.affiliation: †Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, United States.|‡Department of Pharmaceutics, School of Pharmacy, Fudan University, and Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Shanghai 201203, People's Republic of China.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Pang
authors.affiliation: †Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, United States.
authors.forename: Che-Ming J
authors.initials: CM
authors.lastname: Hu
authors.affiliation: †Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, United States.
authors.forename: Ronnie H
authors.initials: RH
authors.lastname: Fang
authors.affiliation: †Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, United States.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Luk
authors.affiliation: †Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, United States.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Gao
authors.affiliation: †Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, United States.|‡Department of Pharmaceutics, School of Pharmacy, Fudan University, and Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Shanghai 201203, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: †Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, United States.
authors.forename: Erdembileg
authors.initials: E
authors.lastname: Chuluun
authors.affiliation: †Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, United States.
authors.forename: Pavimol
authors.initials: P
authors.lastname: Angsantikul
authors.affiliation: †Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, United States.
authors.forename: Soracha
authors.initials: S
authors.lastname: Thamphiwatana
authors.affiliation: ‡Department of Pharmaceutics, School of Pharmacy, Fudan University, and Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Shanghai 201203, People's Republic of China.
authors.forename: Weiyue
authors.initials: W
authors.lastname: Lu
authors.affiliation: ‡Department of Pharmaceutics, School of Pharmacy, Fudan University, and Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Shanghai 201203, People's Republic of China.
authors.forename: Xinguo
authors.initials: X
authors.lastname: Jiang
authors.affiliation: †Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, United States.
authors.forename: Liangfang
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D040761:Biomimetic Materials / Q000737:chemistry / Q000494:pharmacology*; D004006:Dichlorvos / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D053758:Nanoparticles / Q000737:chemistry*; D062025:Organophosphate Poisoning / Q000188:drug therapy*
chemical_list: D004006:Dichlorvos; D000110:Acetylcholinesterase
keywords: acetylcholinesterase; biodetoxification; biomimetic nanoparticle; nanomedicine; organophosphate