Hemoglobin-based oxygen carriers with antioxidant properties

Abstract

Hemoglobin (Hb)-based oxygen carriers (HBOCs) are being investigated as therapeutics for the treatment of hemorrhagic shock, when red blood cells (RBCs) are unavailable. Researchers have investigated different techniques to impart antioxidant properties to HBOCs, in order to mitigate oxidative damage observed after hemorrhagic shock resuscitation. In our previous work, we have investigated the coating of Hb with polydopamine (PDA) and have shown that PDA-coated Hb exhibits antioxidant properties while retaining its oxygen transport properties. Since the PDA coating is biodegradable and cell-free Hb in circulation is toxic, in our current study, we explore PDA coating of tense (T-) and relaxed (R-) state polymerized human hemoglobin (PolyHb). Similar to our previous study on PDA coating of CO-bound human Hb, CO binding of T- and R-state PolyHb significantly reduced metHb formation of the PDA coated PolyHb. PDA coating of PolyHb resulted in enhanced antioxidant properties of PDA–PolyHb as measured by the reducing power, radical scavenging, ferryl oxidation, and catalase activity. T-state PolyHb demonstrated moderate changes in O₂ transport properties after PDA coating, with both T- and R-state PolyHb exhibiting higher auto-oxidation rates after PDA coating. A slight increase in hydrodynamic diameter and a moderate decrease in thermal stability for both PDA-coated PolyHbs were observed compared to the precursor PolyHbs. T- and R-state PDA-coated PolyHb show promise as potential oxygen carriers with antioxidant properties, yet further optimization is needed to limit changes in oxygen transport properties.