Artificial oxygen carriers, from nanometer- to micrometer-sized particles, made of hemoglobin composites substituting for red blood cells
Source abstract
Abstract
Abstract Blood transfusions are regarded as the most well-known and frequently performed cell transplantations. Although current transfusion systems are sophisticated, they cannot be freed from the inherent difficulties that include infection, short shelf life, and blood type mismatching. Artificial oxygen carriers produced using hemoglobin (Hb) are designated as Hb-based oxygen carriers (HBOCs), which are anticipated for use as biomaterials that have potential to resolve issues of transfusion by a radical paradigm shift. Various HBOCs, nanometer-sized to micrometer-sized bioparticles having an oxygen-carrying function, are developed for use as substitutes for red blood cells (RBCs). This paper presents an overview of the classification of HBOCs with reference to their histories, preparations, structures, functions, and in vitro and in vivo properties. Additionally, we give a more detailed introduction of our academic studies of liposome encapsulated Hb, designated as Hb-vesicles (HbV), which mimic the physiologically important corpuscular structure of RBCs. This review outlines perennial efforts and approaches to mimic RBC functions through chemical, genetic, and encapsulation techniques. It will provide important insights into the eventual realization of an alternative for RBC transfusion.
Source: openaire · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Hemoglobin structure and function · Erythrocyte Function and Pathophysiology · Neonatal Health and Biochemistry
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (100+)
Show source-provided references
1. PEGylated bovine carboxyhemoglobin (SANGUINATE™): Results of clinical safety testing and use in patients10.1007/978-1-4939-3023-4_58 ↗
2. SANGUINATE (PEGylated carboxyhemoglobin bovine): Mechanism of action and clinical update10.1111/aor.12934 ↗
3. Design of nonhypertensive conjugated hemoglobin as novel resuscitation fluids
4. HemoLink™, an O-raffinose cross-linked hemoglobin-based oxygen carrier
5. Mechanisms of toxicity and modulation of hemoglobin-based oxygen carriers10.1097/SHK.0000000000001044 ↗
6. Polymersome encapsulated hemoglobin: A novel type of oxygen carrier10.1021/bm0501454 ↗
7. Hemoglobin-dialdehyde dextran conjugates: Improvement of their oxygen-binding properties with anionic groups10.1007/BF01886853 ↗
8. O-raffinose cross-linked hemoglobin lacks site-specific chemistry in the central cavity: Structural and functional consequences of β93Cys modification10.1002/prot.20453 ↗
9. Interaction of haptoglobin with hemoglobin octamers based on the mutation α Asn78Cys or β Gly83Cys10.4236/ajmb.2012.21001 ↗
10. Genetically cross-linked hemoglobin: A structural study
11. Positive and negative cooperativities at subsequent steps of oxygenation regulate the allosteric behavior of multistate sebacylhemoglobin10.1021/bi952446b ↗
12. Development of zero-link polymers of hemoglobin, which do not extravasate and do not induce pressure increases upon infusion10.1080/10731190600974277 ↗
13. Chemical characterization of diaspirin cross-linked hemoglobin polymerized with poly(ethylene glycol)10.1021/ac060188q ↗
14. Overview of the effects of diaspirin cross-linked hemoglobin (DCLHb) on oxygenation, perfusion of the microcirculation and clinical studies
15. PEGylation promotes hemoglobin tetramer dissociation10.1021/bc900130f ↗
16. The effects of stroma-free and dextran-conjugated hemoglobin on hemodynamics and carotid blood flow in hemorrhaged guinea pigs10.3109/10731199909117483 ↗
17. Therapeutic applications of polymeric artificial cells10.1038/nrd1659 ↗
18. Isolation and characterization of a new hemoglobin derivative cross-linked between the α chains (Lysine 99α1 → Lysine 99α2)10.1016/S0021-9258(18)67605-7 ↗
19. Current development and use of hemoglobin-based oxygen-carrying (HBOC) solutions10.1046/j.1435-6935.2003.00084.x ↗
20. Lipid encapsulated hemoglobin as a synthetic erythrocyte
21. Biophysical properties of Lumbricus terrestris erythrocruorin and its potential use as a red blood cell substitute10.3390/jfb3010049 ↗
22. Does prolonged storage of red blood cells cause harm?10.1111/bjh.12747 ↗
23. Effects of free and liposome-encapsulated hemoglobin on choroidal vascular plexus blood flow, using the rabbit eye as a model system10.1177/112067219900900206 ↗
24. Recent progress in the development of recombinant human hemoglobin (rHb1.1) as an oxygen therapeutic
25. Hemoglobin–albumin clusters prepared using N-succinimidyl 3-maleimidopropionate as an appropriate cross-linker10.1021/acsomega.8b03474 ↗
26. Genetically engineered haemoglobin wrapped covalently with human serum albumins as an artificial O2 carrier10.1039/C9TB02184A ↗
27. Encapsulation of hemoglobin in phospholipid vesicles10.1016/0014-5793(83)80625-5 ↗
28. Novel nanodimension artificial red blood cells that act as O2 and CO2 carrier with enhanced antioxidant activity: PLA-PEG nanoencapsulated polySFHb-superoxide dismutase-catalase-carbonic anhydrase10.3109/21691401.2012.751180 ↗
29. In vivo evaluation of electron mediators for the reduction of methemoglobin encapsulated in liposomes using electron energies produced by red blood cell glycolysis10.1080/21691401.2017.1397003 ↗
30. The development of hemoglobin solutions as red cell substitutes: Hemoglobin solutions10.1016/0955-3886(95)93436-A ↗
31. The life-sustaining capacity of human polymerized hemoglobin when red cells might be unavailable10.1016/S1072-7515(02)01335-2 ↗
32. Intraosseous transfusion of hemoglobin vesicles in the treatment of hemorrhagic shock with collapsed vessels in a rabbit model10.1111/trf.15915 ↗
33. Polymerization of diaspirin cross-linked hemoglobin (DCLHb) with water-soluble, nonimmunogenic polyamide cross-linking agents10.1021/bc9900486 ↗
34. Polymerization of diaspirin cross-linked hemoglobin (DCLHb) with PEG activated with benzenesulfonate bearing electron-withdrawing groups10.1016/S0040-4020(98)01230-7 ↗
35. Synthesis of hemoglobin-based oxygen carrier nanoparticles by desolvation precipitation10.1021/acs.langmuir.0c01698 ↗
36. A solid phase adsorption method for preparation of bovine serum albumin-bovine hemoglobin conjugate10.1016/S0168-1656(02)00246-8 ↗
37. Propylbenzmethylation at Val-1(α) markedly increases the tetramer stability of the PEGylated hemoglobin: A comparison with propylation at Val-1(α)10.1016/j.bbagen.2012.09.013 ↗
38. Iwasaki · Artificial Cells, Nanomedicine, and Biotechnology · 2018 · 46 · S62110.1080/21691401.2018.1505740 ↗
39. Pyridoxalated hemoglobin-polyoxyethylene conjugate (PHP) as an oxygen carrier
40. A new resuscitation fluid “stabilized hemoglobin” preparation and characteristics10.3109/10731198809132576 ↗
41. Blood substitutes as pharmacotherapies in clinical practice10.1097/ACO.0b013e328172225a ↗
42. Cross-linked, polymerized, and PEG-conjugated hemoglobin-based oxygen carriers: Clinical safety and efficacy of recent and current products10.2174/157016312802650742 ↗
43. Polyethylene glycol camouflaged earthworm hemoglobin10.1371/journal.pone.0170041 ↗
44. Affinity labeling of hemoglobin with 4,4’-diisothiocyanostilbene-2,2’-disulfonate: Covalent cross-linking in the 2,3-diphosphoglycerate binding site10.1021/bi00405a062 ↗
45. Potential electron mediators to extract electron energies of RBC glycolysis for prolonged in vivo functional lifetime of hemoglobin-vesicles10.1021/acs.bioconjchem.5b00076 ↗
46. Site-directed mutagenesis of cysteine residues alters oxidative stability of fetal hemoglobin10.1016/j.redox.2018.08.010 ↗
47. Three-point cross-linking: Potential red cell substitutes from the reaction of trimesoyl tris(methyl phosphate) with hemoglobin10.1021/bi00148a016 ↗
48. Connecting proteins by design. Cross-linked bis-hemoglobin10.1021/ja9910107 ↗
49. Effect of hemoglobin vesicle, a cellular-type artificial oxygen carrier, on middle cerebral artery occlusion- and arachidonic acid-induced stroke models in rats10.1016/j.neulet.2007.04.080 ↗
50. Preparation of artificial red blood cells (hemoglobin vesicles) using the rotation-revolution mixer for high encapsulation efficiency10.1021/acsbiomaterials.1c00424 ↗
51. Size‐dependent interaction of cells and hemoglobin–albumin based oxygen carriers prepared using the SPG membrane emulsification technique10.1002/btpr.2170 ↗
52. Preparation of uniform-sized hemoglobin–albumin microspheres as oxygen carriers by Shirasu porous glass membrane emulsification technique10.1016/j.colsurfb.2015.01.018 ↗
53. First-in-human use of a marine oxygen carrier (M101) for organ preservation: A safety and proof-of-principle study10.1111/ajt.15798 ↗
54. Artificial oxygen carriers rescue placental hypoxia and improve fetal development in the rat pre-eclampsia model
55. Polymerized human placenta hemoglobin improves resuscitative efficacy of hydroxyethyl starch in a rat model of hemorrhagic shock10.3109/21691401.2015.1024846 ↗
56. Preparation and characterization of liposome-encapsulated haemoglobin by a freeze-thaw method10.3109/02652049409034258 ↗
57. Low-fouling electrosprayed hemoglobin nanoparticles with antioxidant protection as promising oxygen carriers10.1002/mabi.201900293 ↗
58. Conjugation of multiple copies of polyethylene glycol to hemoglobin facilitated through thiolation: Influence on hemoglobin structure and function10.1007/s10930-005-7837-2 ↗
59. Vascular response to infusions of a nonextravasating hemoglobin polymer10.1152/japplphysiol.00191.2002 ↗
60. Entropy-driven supramolecular ring-opening polymerization of a cyclic hemoglobin monomer for constructing a hemoglobin−PEG alternating polymer with structural regularity10.1021/acs.biomac.1c00061 ↗
61. Analysis of dimeric αβ subunit exchange between PEGylated and native hemoglobins (α2β2 tetramer) in an equilibrated state by intramolecular ββ-cross-linking10.1021/acs.biomac.8b00728 ↗
62. Ring-opening polymerization of hemoglobin10.1021/acs.biomac.8b01789 ↗
63. PEGylated carboxyhemoglobin bovine (SANGUINATE): Results of a phase I clinical trial10.1111/aor.12341 ↗
64. A Phase Ib open label, randomized, safety study of SANGUINATE™ in patients with sickle cell anemia10.1016/j.bjhh.2016.08.004 ↗
65. Preparation and surface characterization of carboxymethylchitin-incorporated submicron bilayer-lipid membrane artificial cells (liposomes) encapsulating hemoglobin10.3109/10731199109117851 ↗
66. Synthetic approaches to RBC mimicry and oxygen carrier systems10.1021/bm400074t ↗
67. Haemoglobin(βK120C)–albumin trimer as an artificial O2 carrier with sufficient haemoglobin allostery10.1039/D0CB00056F ↗
68. Safety profile of high molecular weight polymerized hemoglobins10.1111/trf.16157 ↗
69. Coronary vascular bed perfusion with a polyethylene glycol-modified hemoglobin-encapsulated liposome, neo red cell, in rats10.1046/j.1525-1594.1998.05092.x ↗
70. Cell-free hemoglobin-based blood substitutes and risk of myocardial infarction and death: A meta-analysis10.1001/jama.299.19.jrv80007 ↗
71. Potential new non-invasive therapy using artificial oxygen carriers for pre-eclampsia10.3390/jfb8030032 ↗
72. Development of human-derived hemoglobin-albumin microspheres as oxygen carriers using Shirasu porous glass membrane emulsification10.1016/j.jbiosc.2018.04.017 ↗
73. A multicenter clinical study of the safety and activity of maleimide-polyethylene glycol-modified Hemoglobin (Hemospan) in patients undergoing major orthopedic surgery10.1097/00000542-200612000-00015 ↗
74. Bis[2-(4-carboxyphenoxy)carbonylethyl]phosphinic acid (BCCEP): A new reagent for hemoglobin modification10.3109/10731199709117448 ↗
75. Hemoglobin vesicles improve wound healing and tissue survival in critically ischemic skin in mice10.1152/ajpheart.00430.2009 ↗
76. Simple method for preparing poly(ethylene glycol)-surface-conjugated liposome-encapsulated hemoglobins: Physicochemical properties, long-term storage stability, and their reactions with O2, CO, and NO10.1021/la201246m ↗
77. Reactivity of polymersome encapsulated hemoglobin with physiologically important gaseous ligands: Oxygen, carbon monoxide, and nitric oxide10.1021/ma202739f ↗
78. Influence of nanotechnology to combat against COVID-19 for global health emergency: A review10.1016/j.sintl.2020.100079 ↗
79. Physicochemical properties and oxygen affinity of glutaraldehyde polymerized crocodile hemoglobin: the new alternative hemoglobin source for hemoglobin-based oxygen carriers10.1080/21691401.2019.1579733 ↗
80. Arenicola marina extracellular hemoglobin: A new promising blood substitute10.1002/biot.200500049 ↗
81. Low resolution crystal structure of Arenicola erythrocruorin: Influence of coiled coils on the architecture of a megadalton respiratory protein10.1016/j.jmb.2006.10.016 ↗
82. Surface modification of hemoglobin vesicles with poly(ethylene glycol) and effects on aggregation, viscosity, and blood flow during 90% exchange transfusion in anesthetized rats10.1021/bc960069p ↗
83. Molecular dimensions of Hb-based O2 carriers determine constriction of resistance arteries and hypertension10.1152/ajpheart.2000.279.3.H908 ↗
84. Haemoglobin-vesicles as artificial oxygen carriers: Present situation and future visions10.1111/j.1365-2796.2007.01893.x ↗
85. Red blood cells donate electrons to methylene blue mediated chemical reduction of methemoglobin compartmentalized in liposome in blood10.1021/bc500153x ↗
86. Fluid resuscitation with artificial oxygen carriers in hemorrhaged rats: Profiles of hemoglobin-vesicle degradation and hematopoiesis for 14 days10.1097/SHK.0b013e31817d4066 ↗
87. Hemoglobin-vesicles as an artificial oxygen carrier10.1016/S0076-6879(09)65019-9 ↗
88. A clinical safety trial of stroma-free hemoglobin10.1002/cpt197823173 ↗
89. Synthesis and characterisation of aqueous haemoglobin-based microcapsules coated by genipin-cross-linked albumin10.1080/02652048.2020.1715498 ↗
90. Preparation and in vitro characteristics of polymerized pyridoxylated hemoglobin10.1046/j.1537-2995.1983.23283172857.x ↗
91. Artificial red blood cells increase large vessel wall damage and decrease surrounding dermal tissue damage in a rabbit auricle model after subsequent flashlamp-pumped pulsed-dye laser treatment10.1111/1346-8138.15805 ↗
92. Shock index and prediction of traumatic hemorrhagic shock 28-day mortality: Data from the DCLHb resuscitation clinical trials10.5811/westjem.2014.7.21304 ↗
93. Potential mechanism of dextran-conjugated hemoglobin penetration inside arterial wall
94. Hemolytic transfusion reactions10.1159/000154811 ↗
95. Pharmacokinetic study of enclosed hemoglobin and outer lipid component after the administration of hemoglobin vesicles as an artificial oxygen carrier10.1124/dmd.109.027094 ↗
96. Myocardial electrical remodeling and the arrhythmogenic substrate in hemorrhagic shock-induced heart: Anti-arrhythmogenic effect of liposome-encapsulated hemoglobin (HbV) on the myocardium10.1097/SHK.0000000000001262 ↗
97. Long-term stored hemoglobin-vesicles, a cellular type of hemoglobin-based oxygen carrier, has resuscitative effects comparable to that for fresh red blood cells in a rat model with massive hemorrhage without post-transfusion lung injury10.1371/journal.pone.0165557 ↗
98. Covalent core-shell architecture of hemoglobin and human serum albumin as an artificial O2 carrier10.1021/bm400204y ↗
99. Artificial oxygen carriers, hemoglobin vesicles and albumin-hemes, based on bioconjugate chemistry10.1021/bc800431d ↗
100. How cell number and cellular properties of blood-banked red blood cells of different cell ages decline during storage10.1371/journal.pone.0105692 ↗