Synthesis of bioactive hemoglobin-based oxygen carrier nanoparticles via metal-phenolic complexation

The transfusion of donor red blood cells (RBCs) is seriously hampered by important drawbacks that include limited availability and portability, the requirement of being stored in refrigerated conditions, a short shelf life or the need for RBC group typing and crossmatching. Thus, hemoglobin (Hb)-based oxygen (O 2 ) carriers (HBOCs) which make use of the main component of RBCs and the responsible protein for O 2 transport, hold a lot of promise in modern transfusion and emergency medicine. Despite the great progress achieved, it is still difficult to create HBOCs with a high Hb content to attain the high O 2 demands of our body. Herein a metal–phenolic self-assembly approach that can be conducted in water and in one step to prepare nanoparticles (NPs) fully made of Hb (Hb-NPs) is presented. In particular, by combining Hb with polyethylene glycol , tannic acid (TA) and manganese ions , spherical Hb-NPs with a uniform size around 350–525 nm are obtained. The functionality of the Hb-NPs is preserved as shown by their ability to bind and release O 2 over multiple rounds. The binding mechanism of TA and Hb is thoroughly investigated by UV–vis absorption and fluorescence spectroscopy . The binding site number, apparent binding constant at two different temperatures and the corresponding thermodynamic parameters are identified. The results demonstrate that the TA-Hb interaction takes place through a static mechanism in a spontaneous process as shown by the decrease in Gibbs free energy . The associated increase in entropy suggests that the TA-Hb binding is dominated by hydrophobic interactions.