Detoxification of Organophosphate Poisoning Using Nanoparticle Bioscavengers.
Detoxification of Organophosphate Poisoning Using Nanoparticle Bioscavengers.
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DOI：
10.1021/acsnano.5b02132
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发表时间：
2015-06-23
期刊：
影响因子：
17.1
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Pang Z;Hu CM;Fang RH;Luk BT;Gao W;Wang F;Chuluun E;Angsantikul P;Thamphiwatana S;Lu W;Jiang X;Zhang L
有机磷中毒是高度致命的，因为有机磷通常存在于杀虫剂和神经毒剂中，可引起乙酰胆碱酯酶（AChE）的不可逆磷酸化和失活，通过体内乙酰胆碱的积累导致神经肌肉疾病。因此，直接阻断体循环中的有机磷提供了治疗此病的理想策略。受红细胞（RBC）膜上乙酰胆碱酯酶存在的启发，我们探索了一种由红细胞膜包围的聚合核组成的仿生纳米颗粒，作为抗有机磷剂。通过体外研究，我们证明了仿生纳米颗粒保留了膜结合AChE的酶活性，并能够与模型有机磷敌敌畏结合，从而排除了其对其他酶底物的抑制作用。在有机磷中毒小鼠模型中，纳米颗粒被证明可以改善血液中的乙酰胆碱酯酶活性，并显着提高敌敌畏小鼠的存活率。
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 acetylcholinesterase 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.