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

Abstract

The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10. 1002/mabi.201900293. 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 asprepared 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.

Hemoglobin-Based Oxygen Carriers Incorporating Nanozymes for the Depletion of Reactive Oxygen Species

“…Specifically, individual Hb molecules have been PDAcoated, but also larger particles fully made of Hb. [33][34][35][36] Herein, Hb's coating by PDA was conducted employing a weight ratio 5:1 of Hb and DA for 3 h.…”

Synthesis of Nanoparticles Fully Made of Hemoglobin with Antioxidant Properties: A Step toward the Creation of Successful Oxygen Carriers

“…To achieve an oxygen-carrying capacity similar to that of blood, carriers with high Hb loading are required since, within native RBCs, Hb comprises about 96% of their dry weight. 15 A promising approach to create HBOCs with a high Hb content is to fabricate solid Hb nanoparticles (NPs). We have recently reported the fabrication of small, solid NPs fully made of Hb (Hb-NPs) using the electrospraying technique, resulting in Hb-NPs with a diameter ranging from 370 to 480 nm.…”

“…We have recently reported the fabrication of small, solid NPs fully made of Hb (Hb-NPs) using the electrospraying technique, resulting in Hb-NPs with a diameter ranging from 370 to 480 nm. 15 However, an important drawback of these Hb-NPs is the low throughput of the electrospraying technique, which creates challenges for their production at clinically relevant scales. 16 Using a different approach, the Palmer group was able to synthesize Hb-NPs by borrowing the techniques currently used for the fabrication of protein NPs.…”

Immobilization of BMP-2 and VEGF within Multilayered Polydopamine-Coated Scaffolds and the Resulting Osteogenic and Angiogenic Synergy of Co-Cultured Human Mesenchymal Stem Cells and Human Endothelial Progenitor Cells

“…As a strategy to immobilize GFs onto the scaffolds, we employed self-polymerization of dopamine (DA) into polydopamine (PDA). This in situ self-polymerization process results in a PDA coating which can adhere into virtually any substrate independently of the constituting material, size or shape [ 12 , 20 , 21 , 22 , 23 ]. This results in an efficient strategy to incorporate biomolecules onto different substrates without the need for surface pretreatment [ 12 , 24 ].…”