Artificial oxygen carriers, hemoglobin vesicles and albumin-hemes, based on bioconjugate chemistry.
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 O(2) carriers of two types, which will be useful as transfusion alternatives in clinical situations. Along with sufficient O(2) 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 O(2) 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 O(2) 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 albumin-based O(2) carriers. Changing the chemical structure of incorporated FeP controls O(2) binding parameters. In fact, PEG-modified HSA-FeP showed good blood compatibility and O(2) transport in vivo. Furthermore, the genetically engineered heme pocket in HSA can confer O(2) binding ability to the incorporated natural Fe(2+)protoporphyrin IX (heme). The O(2) 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 O(2).
Tsuchida
Eishun
E
Research Institute for Science and Engineering, Waseda University, Tokyo, Japan. eishun@waseda.jp
Sou
Keitaro
K
Nakagawa
Akito
A
Sakai
Hiromi
H
Komatsu
Teruyuki
T
Kobayashi
Koichi
K
D001802:Blood Substitutes / Q000737:chemistry* / Q000378:metabolism; D006454:Hemoglobins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008665:Metalloporphyrins / Q000737:chemistry* / Q000378:metabolism; D010100:Oxygen / Q000737:chemistry* / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000378:metabolism; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism
D001802:Blood Substitutes; D006454:Hemoglobins; D008665:Metalloporphyrins; D010743:Phospholipids; D012709:Serum Albumin; D011092:Polyethylene Glycols; D010100:Oxygen