Oxygen Carriers

Gupta, Anirban Sen; Doctor, Allan

doi:10.1007/978-3-030-20820-2_11

Cited by 6 publications

(15 citation statements)

References 154 publications

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“…Once in the underlying smooth muscle tissue, the HBOCs can act as NO scavengers and, due to its vasodilatory properties, NO scavenging results in adverse cardiovascular events. 3 However, when too large (i.e., in the range of 1−3 μm), the HBOCs are strongly phagocytosed by the macrophages of the MPS. 34,35 Thus, the size of HBOCs should preferably be in the range from 100 nm to 1 μm.…”

Section: Resultsmentioning

confidence: 99%

“…HBOCs should be large enough to avoid vasoconstriction, hypertension, and short circulation times but, when too small, they can permeate through the gaps in between the endothelial cells lining our blood vessels. Once in the underlying smooth muscle tissue, the HBOCs can act as NO scavengers and, due to its vasodilatory properties, NO scavenging results in adverse cardiovascular events . However, when too large (i.e., in the range of 1–3 μm), the HBOCs are strongly phagocytosed by the macrophages of the MPS. , Thus, the size of HBOCs should preferably be in the range from 100 nm to 1 μm.…”

Section: Results and Discussionmentioning

confidence: 99%

“…Additionally, since NO is an important vasodilator, its sequestration generates vasoconstriction and the subsequent cardiovascular complications, which, paradoxically, diminish the delivery of oxygen into the tissues. 3 Approaches to overcome the limitations of native Hb involve its encapsulation within a protective shell to increase the molecular diameter of Hb and to shield it from permeating through the blood vessels. As such, Hb has already been entrapped within several systems, including liposomes, 10,11 polymeric nanoparticles, 12 or metal−organic frameworks.…”

Section: Introductionmentioning

confidence: 99%

“…Blood transfusions, which usually involve the administration of packed red blood cells (RBCs), are a mainstream procedure used to treat acute blood loss (e.g., due to trauma), severe blood disorders (e.g., anemia or hemophilia), or for patients receiving tumor chemotherapy. , However, unfortunately, using blood from donors also has important limitations: blood is a scarce resource and the declining donor rate together with an increasing demand due to population growth and aging will eventually result in a critical shortage of blood. − Additionally, other important drawbacks of blood are the risks of virus transmission or its short shelf-life; the latter makes it impossible to create large blood stockpiles to be used when acute disasters occur (e.g., earthquakes, terrorist attacks). − …”

Section: Introductionmentioning

confidence: 99%

“…Cell-free Hb has an extremely short circulatory residence time since it is rapidly cleared from circulation by the kidneys and by the mononuclear phagocyte system (MPS) in the spleen and liver. This results in Hb-induced toxicity in these organs. ,, Furthermore, once in the vasculature, cell-free Hb can extravasate into the subendothelial layer, where it rapidly acts as a nitric oxide (NO) scavenger leading to the oxidation of Hb to methemoglobin (metHb). Additionally, since NO is an important vasodilator, its sequestration generates vasoconstriction and the subsequent cardiovascular complications, which, paradoxically, diminish the delivery of oxygen into the tissues …”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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Transfusion of donor red blood cells (RBCs) is a crucial and widely employed clinical procedure. However, important constraints of blood transfusions include the limited availability of blood, the need for typing and cross-matching due to the RBC membrane antigens, the limited storage lifetime, or the risk for disease transmission. Hence, a lot of effort has been devoted to develop RBC substitutes, which are free from the limitations of donor blood. Despite the potential, the creation of hemoglobin (Hb)-based oxygen carriers is still facing important challenges. To allow for proper tissue oxygenation, it is essential to develop carriers with high Hb loading since Hb comprises about 96% of the RBCs’ dry weight. In this work, nanoparticles (NPs) fully made of Hb are prepared by the desolvation precipitation method. Several parameters are screened (i.e., Hb concentration, desolvation ratio, time, and sonication intensity) to finally obtain Hb-NPs with a diameter of ∼568 nm and a polydispersity index (PDI) of 0.2. A polydopamine (PDA) coating is adsorbed to prevent the disintegration of the resulting Hb/PDA-NPs. Due to the antioxidant character of PDA, the Hb/PDA-NPs are able to deplete two harmful reactive oxygen species, namely, the superoxide radical anion and hydrogen peroxide. Such antioxidant protection also translates into minimizing the oxidation of the entrapped Hb to nonfunctional methemoglobin (metHb). This is a crucial aspect since metHb conversion also results in inflammatory reactions and dysregulated vascular tone. Finally, yet importantly, the reported Hb/PDA-NPs are also both hemo- and biocompatible and preserve the reversible oxygen-binding and releasing properties of Hb.

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Section: Resultsmentioning

confidence: 99%

Section: Results and Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

et al. 2021

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Potential Clinical Application of Hemoglobin Vesicles as an Artificial Oxygen Carrier and Carbon Monoxide Carrier

Sakai

Kobayashi²,

Kure³

et al. 2022

Blood Substitutes and Oxygen Biotherapeutics

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Metal-Phenolic Networks as Broad-Spectrum Antioxidant Coatings for Hemoglobin Nanoparticles Working as Oxygen Carriers

et al. 2022

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Timely administration of donor red blood cells (RBCs) is a crucial and life-saving procedure to restore tissue oxygenation in patients suffering from acute blood loss. However, important drawbacks of using allogenic RBCs are their limited availability and portability, specific storage requirements, short shelf life, or the need for blood type matching. These limitations result in serious logistical challenges that make the transfusion of donor RBCs difficult in extreme life-threatening situations prior to hospital admission. Thus, the engineering of hemoglobin (Hb) nanoparticles (Hb-NPs), which are free from the aforementioned limitations, has emerged as a promising strategy to create RBC substitutes to be used when donor blood is not available. Despite the tremendous progress achieved in recent years, many challenges still need to be overcome. For example, it is still difficult to create Hb-NPs with a high Hb content while also preventing the autoxidation of Hb into nonfunctional methemoglobin (metHb). Herein, the fabrication of small, solid Hb-NPs with an antioxidant coating is reported. By desolvation precipitation, Hb-NPs with an average hydrodynamic diameter of ∼250 nm and a polydispersity index of ∼0.2 are fabricated. A metal-phenolic network (MPN) layer consisting of a phenolic ligand (i.e., tannic acid) cross-linked through iron(III) ions is deposited onto the Hb-NPs surface to render antioxidant protection. The resulting MPN-coated Hb-NPs (MPN@Hb-NPs) maintain the ability of the encapsulated Hb to reversibly bind and release oxygen. The antioxidant properties are demonstrated, showing that MPN@Hb-NPs can effectively scavenge multiple reactive oxygen and nitrogen species, both in solution and in the presence of human RBCs and two relevant cell lines, namely, macrophages and endothelial cells. Importantly, these outstanding antioxidant properties resulting from the MPN translate into decreased metHb conversion. Finally, the newly reported MPN@Hb-NPs are also biocompatible, as shown by hemolysis rate and cell viability studies and can be used to protect the cells from oxidative damage. All in all, we have identified a novel strategy to minimize heme-mediated oxidative reactions that could potentially bring this new generation of Hb-based oxygen carriers a step closer to the clinic.

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Oxygen Carriers

Cited by 6 publications

References 154 publications

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

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

Potential Clinical Application of Hemoglobin Vesicles as an Artificial Oxygen Carrier and Carbon Monoxide Carrier

Metal-Phenolic Networks as Broad-Spectrum Antioxidant Coatings for Hemoglobin Nanoparticles Working as Oxygen Carriers

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