Transfusion
of donor red blood cells (RBCs) is a crucial and widely
employed clinical procedure. However, important constraints of blood
transfusions include the limited availability of blood, the need for
typing and cross-matching due to the RBC membrane antigens, the limited
storage lifetime, or the risk for disease transmission. Hence, a lot
of effort has been devoted to develop RBC substitutes, which are free
from the limitations of donor blood. Despite the potential, the creation
of hemoglobin (Hb)-based oxygen carriers is still facing important
challenges. To allow for proper tissue oxygenation, it is essential
to develop carriers with high Hb loading since Hb comprises about
96% of the RBCs’ dry weight. In this work, nanoparticles (NPs)
fully made of Hb are prepared by the desolvation precipitation method.
Several parameters are screened (i.e., Hb concentration, desolvation
ratio, time, and sonication intensity) to finally obtain Hb-NPs with
a diameter of ∼568 nm and a polydispersity index (PDI) of 0.2.
A polydopamine (PDA) coating is adsorbed to prevent the disintegration
of the resulting Hb/PDA-NPs. Due to the antioxidant character of PDA,
the Hb/PDA-NPs are able to deplete two harmful reactive oxygen species,
namely, the superoxide radical anion and hydrogen peroxide. Such antioxidant
protection also translates into minimizing the oxidation of the entrapped
Hb to nonfunctional methemoglobin (metHb). This is a crucial aspect
since metHb conversion also results in inflammatory reactions and
dysregulated vascular tone. Finally, yet importantly, the reported
Hb/PDA-NPs are also both hemo- and biocompatible and preserve the
reversible oxygen-binding and releasing properties of Hb.