有机磷化合物生物清除剂及其递送技术研究进展

Research progress in organophosphorus compound bioscavenger and its delivery technology

有机磷神经性毒剂中毒快、致死率高、致死剂量低,在化学武器中占据主要地位。对有机磷神经性毒剂中毒的长效预防、高效治疗以及残存毒剂的彻底清除一直是研究人员关注的焦点。生物清除剂包括具有生物活性的酶和抗体等,按作用机制主要分为与有机磷化合物按摩尔比1∶1定量结合的化学计量型、需与肟类化合物联合使用达到类似“催化作用”的假催化型和利用酶的催化特性快速水解有机磷化合物的催化型。生物清除剂作用高效、迅速,但用作有机磷抗毒剂时往往因其异源蛋白属性而显示出免疫原性,或因稳定性不佳而在体内被迅速清除,亟需通过递送技术予以解决,主要包括聚羧基甜菜碱、聚乙二醇、聚唾液酸修饰及红细胞膜递送和脂质体负载等。本文介绍了有机磷生物清除剂的种类和作用机制,并对有助于提高其成药性的递送技术进行综述,以期为有机磷化合物中毒的预防和治疗提供参考。

Organophosphorus nerve agents dominate chemical weapons because of their rapid poisoning,high mortality and low lethal doses.The long-term prevention,effective treatment and com⁃plete residue removal of nerve agents have been a focus of research.Bioscavengers including enzymes and antibodies with biological activity act efficiently and rapidly.However,when used as an organophosphorus antitoxin,bioscavengers usually show immunogenicity due to their heterologous protein properties,and are quickly eliminated due to their poor stability in vivo,which needs to be resolved by drug delivery technologies including polycarboxybetaine modification,polyethylene glycol modification,polysialic acid modification,red blood cell membrane delivery,and liposome loading.This paper introduces the types and action mechanisms of organophosphorus bioscavengers,and reviews the drug delivery technologies that help to improve their druggability.