TY - JOUR

T1 - Hemoglobin-based oxygen carriers camouflaged with membranes extracted from red blood cells

T2 - Optimization and assessment of functionality

AU - Jansman, Michelle Maria Theresia

AU - Coll-Satue, Clara

AU - Liu, Xiaoli

AU - Kempen, Paul Joseph

AU - Andresen, Thomas Lars

AU - Thulstrup, Peter Waaben

AU - Hosta-Rigau, Leticia

PY - 2022/3

Y1 - 2022/3

N2 - Despite being an indispensable clinical procedure, the transfusion of donor blood has important limitations including a short shelf-life, limited availability and specific storage requirements. Therefore, a lot of effort has been devoted to developing hemoglobin (Hb)-based oxygen carriers (HBOCs) that are able to replace or complement standard blood transfusions, especially in extreme life-threatening situations. Herein, we employed a Hb-loaded poly(lactide-co-glycolide) core which was subsequently coated with nanozymes to protect the encapsulated Hb from oxidation by reactive oxygen species. To render HBOCs with long circulation in the vasculature, which is a crucial requirement to achieve the high oxygen demands of our organism, the carrier was coated with a red blood cell-derived membrane. Three coating methods were explored and evaluated by their ability to repel the deposition of proteins and minimize their uptake by an endothelial cell line. Preservation of the oxygen carrying capacity of the membrane-coated carrier was demonstrated by an oxygen binding and releasing assay and, the functionality resulting from the entrapped nanozymes, was shown by means of superoxide radical anion and hydrogen peroxide depletion assays. All in all, we have demonstrated the potential of the membrane-coated nanocarriers as novel oxygen carrying systems with both antioxidant and stealth properties.

AB - Despite being an indispensable clinical procedure, the transfusion of donor blood has important limitations including a short shelf-life, limited availability and specific storage requirements. Therefore, a lot of effort has been devoted to developing hemoglobin (Hb)-based oxygen carriers (HBOCs) that are able to replace or complement standard blood transfusions, especially in extreme life-threatening situations. Herein, we employed a Hb-loaded poly(lactide-co-glycolide) core which was subsequently coated with nanozymes to protect the encapsulated Hb from oxidation by reactive oxygen species. To render HBOCs with long circulation in the vasculature, which is a crucial requirement to achieve the high oxygen demands of our organism, the carrier was coated with a red blood cell-derived membrane. Three coating methods were explored and evaluated by their ability to repel the deposition of proteins and minimize their uptake by an endothelial cell line. Preservation of the oxygen carrying capacity of the membrane-coated carrier was demonstrated by an oxygen binding and releasing assay and, the functionality resulting from the entrapped nanozymes, was shown by means of superoxide radical anion and hydrogen peroxide depletion assays. All in all, we have demonstrated the potential of the membrane-coated nanocarriers as novel oxygen carrying systems with both antioxidant and stealth properties.

KW - Blood substitutes

KW - Hemoglobin-based oxygen carriers

KW - Cerium oxide nanoparticles

KW - Nanozymes

KW - Red blood cell membrane

KW - Reactive oxygen species

KW - Stealth coatings

KW - SUPEROXIDE-DISMUTASE

KW - POLY(ETHYLENE GLYCOL)

KW - SECONDARY-STRUCTURE

KW - NANOPARTICLES

KW - CATALASE

KW - DEGRADATION

KW - ADSORPTION

KW - MARKER

KW - SELF

U2 - 10.1016/j.msec.2022.112691

DO - 10.1016/j.msec.2022.112691

M3 - Journal article

C2 - 35581082

VL - 134

JO - Biomaterials advances

JF - Biomaterials advances

M1 - 112691

ER -