高铁血红蛋白
解毒剂
化学
氰化物中毒
氰化物
羟钴胺
药理学
血红蛋白
毒性
生物化学
医学
有机化学
维生素B12
氰钴胺
作者
Yuto Suzuki,Kazuaki Taguchi,Tomoko Nishida,Hiromi Sakai,Yuki Enoki,Masaki Otagiri,Kazuaki Matsumoto
标识
DOI:10.1016/j.jconrel.2021.07.015
摘要
Cyanide induces acute lethal poisoning resulting from inhibition of cytochrome c oxidase located in the complex IV (Complex IV) of mitochondria. However, current therapies for cyanide poisoning using hydroxocobalamin and nitrous acid compounds remain a clinical issue. Here, we show that liposome-encapsulated methemoglobin ([email protected]), nanosized biomimetic red blood cells, replicate the antidotal mechanism of nitrous acid compounds against cyanide poisoning, achieving superior efficacy and fast action with no adverse effects. The structure of [email protected], which consists of concentrated methemoglobin in its aqueous core and a lipid membrane resembling the red blood cell membrane, provides favorable characteristics as a cyanide antidote, such as binding properties and membrane permeability. Upon cyanide exposure, [email protected] maintained the mitochondrial function in PC12 cells, resulting in a cell viability comparable to treatment with nitrous acid compounds. In a mouse model of cyanide poisoning, [email protected] treatment dramatically improved mortality with a rapid recovery from the symptoms of cyanide poisoning compared to treatment with nitrous acid compounds. Furthermore, [email protected] also possesses satisfactory pharmacokinetic properties without long-term bioaccumulation and toxicity. Our findings showed a novel concept to develop drugs for cyanide poisoning and provide a promising possibility for biomimetic red blood cell preparations for pharmaceutical applications.
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