Surface-conjugated earthworm mega-hemoglobin as an oxygen therapeutic
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Emergency medical applications involving blood loss frequently require donated blood to enhance oxygen delivery to tissues and restore blood volume in a patient. However, donated blood is in short supply and has complications related to type-matching and blood-transmitted diseases. These limitations have inspired the development of red blood cell alternatives also known as hemoglobin-based oxygen carriers (HBOC). Naturally extracellular hemoglobins, such as that of the earthworm (LtEc), avoid side effects such as extravasation and systemic hypertension associated with transfusion of mammalian derived HBOCs due to their larger size and higher structural stability in the bloodstream. This work focused on surface coating LtEc with oxidized dextran (Odex), an inexpensive, biocompatible polysaccharide, to overcome the potential immune response in vivo. Dextran was functionalized via oxidation then reacted with pure LtEc protein to form Odex-LtEc. Compared to native LtEc, Odex-LtEc showed increased size and molecular weight. Odex-LtEc also had a higher oxygen affinity, slower oxygen offloading rate, and a higher rate of autoxidation. Although certain HBOC characteristics such as increased size are linked to higher stability, animal model trials will be necessary to determine the efficacy of Odex-LtEc in vivo. Reaction conditions may also be further optimized to find a suitable amount of surface coating to retain desirable HBOC characteristics while improving structural stability.