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In the last few decades,hemoglobin(Hb)-based O2 carriers have been developed as a red blood cell(RBC)substitute.However,none satisfies all requirements for clinical use.An important concern(side effect)is increased blood pressure which is caused by NO scavenging by Hb diffused into extra vascular space.More recently,we have synthesized covalent core-shell structured protein clusters of Hb and human serum albumin(HSA)(Hb-HSAm,m=2-4)by linkage of Hb surface lysines to HSA cysteine-34 via an α-succinimidyl-ε-maleimide crosslinker.