Artificial oxygen carriers, hemoglobin vesicles and albumin-hemes, based on bioconjugate chemistry

Eishun Tsuchida, Keitaro Sou, Akito Nakagawa, Hiromi Sakai, Teruyuki Komatsu, Koichi Kobayashi

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Abstract

Hemoglobin (Hb, Mw: 64 500) and albumin (Mw: 66 500) are major protein components in our circulatory system. On the basis of bioconjugate chemistry of these proteins, we have synthesized artificial O2 carriers of two types, which will be useful as transfusion alternatives in clinical situations. Along with sufficient O2 transporting capability, they show no pathogen, no blood type antigen, biocompatibility, stability, capability for long-term storage, and prompt degradation in vivo. Herein, we present the latest results from our research on these artificial O2 carriers, Hb-vesicles (HbV) and albumin-hemes. (i) HbV is a cellular type Hb-based O 2 carrier. Phospholipid vesicles (liposomes, 250 nm diameter) encapsulate highly purified and concentrated human Hb (35 g/dL) to mimic the red blood cell (RBC) structure and eliminate side effects of molecular Hb such as vasoconstriction. The particle surface is modified with PEG-conjugated phospholipids, thereby improving blood compatibility and dispersion stability. Manipulation of physicochemical parameters of HbV, such as O2 binding affinity and suspension rheology, supports the use of HbV for versatile medical applications. (ii) Human serum albumin (HSA) incorporates synthetic Fe 2+porphyrin (FeP) to yield unique albuminbased O2 carriers. Changing the chemical structure of incorporated FeP controls O 2 binding parameters. In fact, PEGmodified HSA-FeP showed good blood compatibility and O2 transport in vivo. Furthermore, the genetically engineered heme pocket in HSA can confer O2 binding ability to the incorporated natural Fe2+protoporphyrin IX (heme). The O2 binding affinity of the recombinant HSA (rHSA)-heme is adjusted to a similar value to that of RBC through optimization of the amino acid residues around the coordinated O2.

Original languageEnglish
Pages (from-to)1419-1440
Number of pages22
JournalBioconjugate Chemistry
Volume20
Issue number8
DOIs
Publication statusPublished - 2009

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ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Organic Chemistry
  • Pharmaceutical Science
  • Biomedical Engineering
  • Pharmacology

Cite this

Tsuchida, E., Sou, K., Nakagawa, A., Sakai, H., Komatsu, T., & Kobayashi, K. (2009). Artificial oxygen carriers, hemoglobin vesicles and albumin-hemes, based on bioconjugate chemistry. Bioconjugate Chemistry, 20(8), 1419-1440. https://doi.org/10.1021/bc800431d