Low-Fouling Electrosprayed Hemoglobin Nanoparticles with Antioxidant Protection as Promising Oxygen Carriers

Despite all the attempts to create advanced hemoglobin (Hb)-based oxygen carriers (HBOCs) employing an encapsulation platform, major challenges including attaining a high Hb loading and long circulation times still need to be overcome. Herein, the fabrication, for the first time, of nanoparticles fully made of Hb (Hb-NPs) employing the electrospray technique is reported. The Hb-NPs are then coated by antioxidant and self-polymerized poly(dopamine) (PDA) to minimize the conversion of Hb into nonfunctional methemoglobin (metHb). The PDA shell is further functionalized with poly(ethylene glycol) (PEG) to achieve stealth properties. The results demonstrate that the as-prepared Hb-NPs are hemo- and biocompatible while offering antioxidant protection and decreasing the formation of metHb. Additionally, decoration with PEG results in decreased protein adsorption onto the Hb-NPs surface, suggesting a prolonged retention time within the body. Finally, the Hb-NPs also preserve the reversible oxygen-binding and releasing properties of Hb. All in all, within this study, a novel HBOCs with high Hb content is fabricated and its potential as an artificial blood substitute is evaluated.