Artificial Oxygen Carriers: An Overview

Artificial oxygen carriers are bioengineered compounds that attempt to replicate the oxygen-delivering capabilities of red blood cells (RBCs). They have the potential to temporarily substitute for red blood cells in patients undergoing hemorrhage or anemia, especially when a typical RBC transfusion is not feasible, such as in field trauma settings, areas where donor blood is limited, and in certain immunocompromised patients.¹

Artificial oxygen carriers are classified according to two types: hemoglobin-based oxygen carriers (HBOCs) and perfluorocarbon-based oxygen carriers (PFCs). HBOCs are derived from purified hemoglobin, usually from human or bovine RBCs, and then chemically modified to prevent the kidney toxicities associated with free hemoglobin in plasma. There are several different possible design approaches to HBOCs: the hemoglobin can exist outside of cells—where the individual hemoglobin subunits may be crosslinked with one another or together crosslinked to a polymer—or encapsulated within a lipid vesicle or another kind of membrane.² Hemopure, for instance, is a cow blood-derived crosslinked molecule linked to the polymer glutaraldehyde; it has been approved in South Africa and Russia but is only available in the United States through the Food and Drug Administration’s Expanded Access Program.³

PFCs, in contrast, are carbon-fluorine compounds capable of dissolving large amounts of oxygen and carbon dioxide. Unlike hemoglobin, which binds oxygen via iron, PFCs carry oxygen by dissolving it. The dissolved oxygen diffuses out of the PFCs when they reach tissues where the oxygen pressure is low, potentially allowing them to reach areas that are inaccessible to RBCs, such as extremely small capillaries.¹

Both HBOCs and PFCs have shown promise as artificial oxygen carriers in clinical and preclinical studies. Several HBOC products, including Hemopure, Hemospan, and Hemassist, have completed phase II trials that demonstrated an increase in oxygen levels.³ PFCs have also given researchers reason to be excited: for instance, one PFC product, a dodecafluoropentane emulsion, demonstrated efficient oxygen delivery at volumes smaller than what is required for traditional PFCs.⁴

However, both classes of artificial oxygen carriers have, in many cases, led to severe side effects, complicating the forward progress of the field. HBOCs, for example, can scavenge nitric oxide in the body, leading to the thinning of blood vessels and potential cardiovascular problems⁵—though the designs of newer versions of HBOCs are meant to reduce this. PFCs can cause flu-like symptoms and, because they are not metabolized in the body, can accumulate in certain tissues and cause toxicities.⁶

There is a great deal of interest in developing safer artificial oxygen carriers, in large part because their use expands beyond trauma care. Recent research has investigated using them in organ transplantation and oncology. There have been reports that HBOCs may help preserve a range of organs during transplantation, including the lungs, kidney, pancreas, and liver.⁷ In oncology, tumor hypoxia (lack of oxygen) can be a barrier to effective radiotherapy, but artificial oxygen carriers could increase oxygen delivery to tumors and reverse this trend.⁸

Before artificial oxygen carriers become part of standard medical care, their safety concerns will first need to be worked out. But if this can happen, there is an enormous amount of potential for them to assume a critical role across a large number of care and patient settings.

References

1. Mohanto, N., Mondal, H., Park, Y.-J. & Jee, J.-P. Therapeutic delivery of oxygen using artificial oxygen carriers demonstrates the possibility of treating a wide range of diseases. Journal of Nanobiotechnology 23, 25 (2025), DOI: 10.1186/s12951-024-03060-9
2. Sen Gupta, A. HEMOGLOBIN-BASED OXYGEN CARRIERS: CURRENT STATE-OF-THE-ART AND NOVEL MOLECULES. Shock 52, 70–83 (2019), DOI: 10.1097/SHK.0000000000001009
3. Chen, L., Yang, Z. & Liu, H. Hemoglobin-Based Oxygen Carriers: Where Are We Now in 2023? Medicina (Kaunas) 59, 396 (2023), DOI: 10.3390/medicina59020396
4. Graham, K., Moon-Massat, P. F. & Unger, E. C. Dodecafluoropentane Emulsion (DDFPE) as a Resuscitation Fluid for Treatment of Hemorrhagic Shock and Traumatic Brain Injury: A Review. Shock 52, 50–54 (2019), DOI: 10.1097/SHK.0000000000001060
5. Kruczkowska, W. et al. The artificial oxygen carrier erythrocruorin—characteristics and potential significance in medicine. J Mol Med (Berl) 101, 961–972 (2023), DOI: 10.1007/s00109-023-02350-3
6. Barbosa, F. T., Jucá, M. J., Castro, A. A., Duarte, J. L. & Barbosa, L. T. Artificial oxygen carriers as a possible alternative to red cells in clinical practice. Sao Paulo Med J 127, 97–100 (2009), DOI: 10.1590/s1516-31802009000200008
7. Sangkum, L., Yang, Z. & Liu, H. Applications of Blood Substitutes in Transplantation Surgery: Where Are We Now? Journal of Anesthesia and Translational Medicine 2, 6–9 (2023), https://doi.org/10.58888/2957-3912-2023-04-002
8. Yu, M., Dai, M., Liu, Q. & Xiu, R. Oxygen carriers and cancer chemo- and radiotherapy sensitization: Bench to bedside and back. Cancer Treatment Reviews 33, 757–761 (2007), DOI: 10.1016/j.ctrv.2007.08.002