Bioconjugation of Serum Albumin to a Maleimide‐appended Porphyrin/Cyclodextrin Supramolecular Complex as an Artificial Oxygen Carrier in the Bloodstream

HemoCD is an inclusion complex of per‐O‐methylated β‐cyclodextrin dimer and an iron(II) porphyrin, which forms a stable O₂ complex in water. Therefore, hemoCD has the potential for use as a synthetic O₂ carrier in mammalian blood. In this study, a hemoCD derivative having a maleimide group (Mal‐hemoCD) was conjugated to a Cys residue of serum albumin via a Michael addition reaction in order to increase the circulation time of the O₂ carrier. The O₂‐binding affinities (P_1/2 Torr]) and half‐lives (t_1/2 h]) of the O₂ adducts at pH 7.4 and 25 °C were determined to be 9 Torr and 23 h for Mal‐hemoCD, and 10 Torr and 14 h for albumin‐conjugated hemoCD (Alb‐hemoCD). Our pharmacokinetic study revealed that renal excretion of Alb‐hemoCD was effectively suppressed and that half of injected Alb‐hemoCD remained in blood at 3 h after injection. It is noteworthy that Mal‐hemoCD also had a long circulation time because of the bioconjugation reaction that occurred during circulation in the bloodstream.