Development of a New Generation of Hemoglobin-Based Oxygen Carriers Using Metal-Organic Frameworks(2/2)

Hemoglobin (Hb), the iron-containing pigment in red blood, is a protein whose major function is to transport oxygen throughout the body. It consists of a tetrameric porphyrin protein comprising two α- and two β-polypeptide chains, each with an iron-containing heme group capable of binding to an oxygen molecule. Hb is contained within erythrocytes (RBC, red blood cell) of which it forms ~33 wt% in normal individuals, a concentration that is nearly the same as that of Hb in its crystalline state. In military as well as civilian traumatic exsanguinating hemorrhage, rapid loss of RBCs can lead to suboptimal tissue oxygenation and subsequent morbidity and mortality. In such cases, transfusion of whole blood or RBCs can significantly improve survival. However, blood products including RBCs present issues of limited availability and portability, need for type-matching, pathogenic contamination risks, and short shelf-life, causing substantial logistical barriers to their prehospital use in austere battlefield and remote civilian conditions. Thus, oxygen carriers have attracted much attention in the areas of biotechnology and modern medicine in recent years; oxygen is not only extremely crucial for human metabolism, but also relevant with the development of many diseases. As the most important oxygen-transporting metalloprotein, Hb has exhibited great potential as an oxygen carrier, generating the so-called “blood substitute”. However, free Hb molecules are unstable once extracted from red blood cells, and the ferrous ion in Hb is easily oxidized into ferric ion in physiological conditions, leading to the irreversible loss of its oxygen-transporting capacity. Therefore, many studies are working towards the bioengineering of semi-synthetic and synthetic surrogates of RBCs using various cross-linked, polymeric, and encapsulated forms of Hb. These Hb-based oxygen carriers (HBOCs) can potentially provide therapeutic oxygenation when blood or RBCs are unavailable. Herein, we have encapsulated Hb into a metal-organic framework (MOF) material. MOFs are a new class of nanoporous materials constructed by metal-based nodes and organic linkers. Owing to their ultrahigh surface area, regular nanostructured pores, tunable pore size, and permanent porosity, MOFs have been used in diverse applications including biosensing, biomass production, and catalysis. In this project, we will establish de novo, water-based, mechanochemical, and ball milling synthetic methods for preparing different biocomposites of Hb embedded into MOFs (Hb@MOFs). In addition, we will elucidate the stability and oxygen-carrying capability of the Hb embedded in our newly synthesized MOF composites in order to further applications in oxygen and antioxidant therapeutics.