Nanoparticle O₂ Carrier Composed of a Polymerized Stroma-Free Hemoglobin Core and Serum Albumin Shell as a Red Blood Cell Alternative in Hemorrhagic Shock Therapy

A wide array of artificial O₂ carriers based on hemoglobin (Hb) has been developed to serve as substitutes for red blood cells (RBCs). Nevertheless, the prevention of heme-iron oxidation within Hb remains a critical challenge. In this study, we synthesized a nanoparticle O₂ carrier comprising a polymerized stromal-free Hb (SFHb) core covered with a human serum albumin shell, designated as SFHbNP. With an optimized particle size of approximately 30 nm, SFHbNPs are engineered to evade uptake by the reticuloendothelial system in various organs. We characterized the physicochemical properties and biochemical functions of SFHbNPs, demonstrating that the incorporation of trace amounts of the antioxidant enzyme catalase within the core effectively suppresses Hb autoxidation. The SFHbNP solution exhibited excellent compatibility with human blood and demonstrated no cytotoxicity toward human endothelial cells. Moreover, its extended circulatory retention enabled preclinical evaluation in animal models. In a rat model of 50% hemorrhagic shock, administration of SFHbNP solution achieved full resuscitation, as evidenced by the restoration of circulatory parameters. Serum biochemistry tests and histopathological analyses of major organs indicated no adverse effects. Comprehensive <i>in vitro</i> and <i>in vivo</i> studies confirm the safety and potential efficacy of SFHbNPs as a promising RBC alternative in transfusion medicine.