Stepping stones to the future of haemoglobin-based blood products: clinical, preclinical and innovative examples

Coll-Satue, Clara; Bishnoi, Shahana; Chen, Jiantao; Hosta‐Rigau, Leticia

doi:10.1039/d0bm01767a

Cited by 23 publications

(26 citation statements)

References 141 publications

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“…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%

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: Introductionmentioning

confidence: 99%

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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“…Therefore, tremendous research efforts have been dedicated to the development of RBCs substitutes in order to avoid the abovementioned drawbacks. 1,3,4 The tetrameric haemoglobin (Hb) protein is the main component of RBCs since it constitutes ~96% of their dry weight content, and is also the responsible molecule for oxygen transport. However, stroma-free Hb cannot be administered into our body due to toxicity issues.…”

Section: Introductionmentioning

confidence: 99%

Metal–organic framework-based oxygen carriers with antioxidant protection as a result of a polydopamine coating

Liu

Jansman

et al. 2021

Biomater. Sci.

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“…The transfusion of donor blood, which usually consists of the administration of packed red blood cells (RBCs), is a widely used and essential procedure for saving lives and maintaining the normal physiological functions of our bodies [1,2]. While the medical demands for blood transfusions are high, donor blood is a scarce resource.…”

Section: Introductionmentioning

confidence: 99%

“…While the chemical modification of Hb can stabilize the tetramer, its covalent modification may impair its cooperativity, affecting its ability to bind and release oxygen. In contrast, the encapsulation platforms protect Hb, by avoiding contact with external stimuli and other blood components, while simultaneously allowing for the incorporation of other compounds within the carrier system [1]. Numerous encapsulation platforms are currently being investigated and, to date, Hb has been successfully entrapped within liposomes, polymersomes, hydrogels, and metal-organic framework-based particles [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Optimization of Hemoglobin Encapsulation within PLGA Nanoparticles and Their Investigation as Potential Oxygen Carriers

et al. 2021

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Hemoglobin (Hb)-based oxygen carriers (HBOCs) display the excellent oxygen-carrying properties of red blood cells, while overcoming some of the limitations of donor blood. Various encapsulation platforms have been explored to prepare HBOCs which aim to avoid or minimize the adverse effects caused by the administration of free Hb. Herein, we entrapped Hb within a poly(lactide-co-glycolide) (PLGA) core, prepared by the double emulsion solvent evaporation method. We study the effect of the concentrations of Hb, PLGA, and emulsifier on the size, polydispersity (PDI), loading capacity (LC), and entrapment efficiency (EE) of the resulting Hb-loaded PLGA nanoparticles (HbNPs). Next, the ability of the HbNPs to reversibly bind and release oxygen was thoroughly evaluated. When needed, trehalose, a well-known protein stabilizer that has never been explored for the fabrication of HBOCs, was incorporated to preserve Hb’s functionality. The optimized formulation had a size of 344 nm, a PDI of 0.172, a LC of 26.9%, and an EE of 40.7%. The HbNPs were imaged by microscopy and were further characterized by FTIR and CD spectroscopy to assess their chemical composition and structure. Finally, the ability of the encapsulated Hb to bind and release oxygen over several rounds was demonstrated, showing the preservation of its functionality.

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Stepping stones to the future of haemoglobin-based blood products: clinical, preclinical and innovative examples

Abstract: Critical overview of the different oxygen therapeutics developed so far to be used when donor blood is not available.

Cited by 23 publications

References 141 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

Metal–organic framework-based oxygen carriers with antioxidant protection as a result of a polydopamine coating

Optimization of Hemoglobin Encapsulation within PLGA Nanoparticles and Their Investigation as Potential Oxygen Carriers

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