Liposome-encapsulated methemoglobin as an antidote against cyanide poisoning

• Published in: Journal of controlled release 2021-09, Vol.337, p.59-70
• Main Authors: Suzuki, Yuto, Taguchi, Kazuaki, Kure, Tomoko, Sakai, Hiromi, Enoki, Yuki, Otagiri, Masaki, Matsumoto, Kazuaki
• Format: Article
• Language: English
• Subjects: Biomimetics; Cyanide poisoning; Liposome; Methemoglobin; Red blood cells
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2021.07.015

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 (metHb@Lipo), 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 metHb@Lipo, 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, metHb@Lipo 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, metHb@Lipo treatment dramatically improved mortality with a rapid recovery from the symptoms of cyanide poisoning compared to treatment with nitrous acid compounds. Furthermore, metHb@Lipo 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. [Display omitted] •metHb@Lipo is encapsulated methemoglobin in liposome, which mimics red blood cell.•metHb@Lipo replicates the antidotal mechanism of nitrite against cyanide poisoning.•metHb@Lipo possesses superior antidotal effect than nitrite and hydroxocobalamin.•metHb@Lipo has favorable pharmacokinetic properties and biocompatibility.