Liposome-encapsulated methemoglobin as an antidote against cyanide poisoning

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.