Liposome-encapsulated methemoglobin as an antidote against cyanide poisoning

Yuto Suzuki, Kazuaki Taguchi, Tomoko Kure, Hiromi Sakai, Yuki Enoki, Masaki Otagiri, Kazuaki Matsumoto

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)59-70
Number of pages12
JournalJournal of Controlled Release
Volume337
DOIs
Publication statusPublished - 2021 Sep 10

Keywords

  • Biomimetics
  • Cyanide poisoning
  • Liposome
  • Methemoglobin
  • Red blood cells

ASJC Scopus subject areas

  • Pharmaceutical Science

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