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Oxygen is necessary for life and plays a key pivotal in maintaining normal physiological functions and treat of diseases. Hemoglobin-based oxygen carriers (HBOCs) have been studied and developed as a replacement for red blood cells (RBCs) in oxygen transport due to their similar oxygen-carrying capacities. However, applications of HBOCs are hindered by vasoactivity, oxidative toxicity, and a relatively short circulatory half-life. With advancements in nanotechnology, Hb encapsulation, absorption, bioconjugation, entrapment, and attachment to nanomaterials have been used to prepare nanomaterial-related HBOCs to address these challenges and pend their application in several biomedical and therapeutic contexts. This review focuses on the progress of this class of nanomaterial-related HBOCs in the fields of hemorrhagic shock, ischemic stroke, cancer, and wound healing, and speculates on future research directions. The advancements in nanomaterial-related HBOCs are expected to lead significant breakthroughs in blood substitutes, enabling their widespread use in the treatment of clinical diseases. [ABSTRACT FROM AUTHOR]

Oxidative toxicity has impeded the development of haemoglobin-based oxygen carriers (HBOCs) by causing methaemoglobin (MetHb) formation and inducing oxidative stress. In our previous work, polydopamine-coated haemoglobin (Hb-PDA) nanoparticles have been designed and synthesized with the capacity to reduce oxidative toxicity. In this investigation, the mass ratio of dopamine (DA) to haemoglobin (Hb) and the pH value are found to be the primary factors that influence preparation of Hb-PDA nanoparticles. X-ray photoelectron spectroscopy showed that the catechol groups of DA play a crucial role in the modification of Hb surface. Hb-PDA nanoparticles were found to exhibit oxidative protection from hydrogen peroxide (H2O2) and the change of mitochondrial membrane potential showed that the Hb-PDA nanoparticles reduced H2O2-induced apoptosis. It is demonstrated that modification of PDA could maintain the oxygen-release capacity of Hb. These findings confirm that Hb-PDA nanoparticles possess restrained oxidative toxicity and preserve oxygen-release capacity. [ABSTRACT FROM AUTHOR]

Hemoglobin (Hb)-based oxygen carriers (HBOCs) have been used as blood substitutes in surgery medicine and oxygen therapeutics for ischemic stroke. As a potent HBOC, the PEGylated Hb has received much attention for its oxygen delivery and plasma expanding ability. Two PEGylated Hbs, Euro-Hb, and MP4 have been developed for clinical trials, using human adult hemoglobin (HbA) as the original substrate. However, HbA was obtained from outdated human blood and its quantity available from this source may not be sufficient for mass production of PEGylated HbA. In contrast, bovine Hb (bHb) has no quantity constraints for its ample resource. Thus, bHb is of potential to function as an alternative substrate to obtain a PEGylated bHb (bHb-PEG). bHb-PEG was prepared under the same reaction condition as HbA-PEG, using maleimide chemistry. The structural, functional, solution and physiological properties of bHb-PEG were determined and compared with those of HbA-PEG. bHb-PEG showed higher hydrodynamic volume, colloidal osmotic pressure, viscosity and P50 than HbA-PEG. The high P50 of bHb can partially compensate the PEGylation-induced perturbation in the R to T state transition of HbA. bHb-PEG was non-vasoactive and could efficiently recover the mean arterial pressure of mice suffering from hemorrhagic shock. Thus, bHb-PEG is expected to function as a potent HBOC for its high oxygen delivery and strong plasma expanding ability. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:252-260, 2017 [ABSTRACT FROM AUTHOR]

The hypoxic environment of tumor may retard the efficacy of tumor therapeutic agents. Hemoglobin (Hb)-based oxygen carriers (HBOCs) could overcome the hypoxia of tumor by the oxygen delivery. However, typical HBOCs may not provide sufficient oxygen for their low oxygen transferring efficiency (OTE). In order to increase the OTE, human adult Hb (HbA) was subjected to triple modifications, i.e., αα-fumaryl crosslink at Lys-99(α), carboxymethylation at Val-1(α) and 8-arm PEG-based polymerization. Crosslink at Lys-99(α) and carboxymethylation at Val-1(α) synergistically led to a T-like quaternary structure of HbA. The dual modification significantly increased the partial oxygen pressure at 50% saturation (P 50) of HbA from 14.8 mmHg to 34.6 mmHg and OTE from 9.1% to 33.1%. Eight-arm PEG-based polymerization slightly decreased the P 50 of the Hb derivative to 27.8 mmHg and OTE to 30.5%. However, it can enlarge the molecular size of HbA and then prolong the serum duration of HbA. The triple modifications synergistically increased the autoxidation rate of Hb, which promote the production of reactive oxygen species (ROS). Therefore, the sufficient oxygen delivery and substantial production of ROS by the triply modified Hb may provide a potential strategy for tumor therapy. [ABSTRACT FROM AUTHOR]

Templated assembly techniques have been extensively used to develop various types of hemoglobin (Hb) loaded particles with improved performance. However, several instability issues must still be solved, including Hb exposure, enhanced Hb auto-oxidation, and the relatively weak binding of Hb to cross-linkers. Herein, to meet the stability requirements for novel hemoglobin-based oxygen carriers (HBOCs), hemoglobin-polydopamine particles (Hb-PDA) were fabricated using a mild process that combines the co-precipitation of Hb and an inorganic template with the spontaneous adhesion of PDA. The Hb-PDA showed uniform size distribution, chemical integrity of both Hb and PDA, high biocompatibility, and robust oxygen delivery. Our results demonstrated that the use of polydopamine as a biocompatible coating material reduced Hb leakage from the particles under both static and flow conditions, thus mitigating the toxicity associated with free Hb and strengthening the stability of Hb particles. In addition, Hb-PDA reduced HUVEC (Human Umbilical Vein Cells) oxidative injury and scavenged 85% of the available hydroxyl radicals, exhibiting its potential to act as an antioxidant for encapsulated Hb. Hb-PDA therefore shows significant promise as a cell-like structurally and functionally stable HBOCs. [ABSTRACT FROM AUTHOR]

Although many attempts have been made to design advanced hemoglobin-based oxygen carriers (HBOCs), no clinically viable product has been widely approved, because they do not perform normal blood functions, such as coagulation, hematologic reactions and stability. Additionally, the in vivo oxygenation of hemoglobin-loaded nanoparticles (HbPs) encapsulated with polymers has seldom been proved. Herein, HbPs of approximately 200 nm with good stability were successfully fabricated and exhibited oxygen-carrying capacity. The HbPs preserve the biological and structure features of hemoglobin according to UV–vis spectrophotometry, Fourier transform infrared (FTIR) spectroscopy and circular dichroism (CD) spectral analysis. In vitro, the HbPs showed a viscosity comparable to that of blood with no obvious effects on red blood cell aggregation. At the same time, blood compatibility was characterized in terms of platelet function, clot strength, speed of clot formation, degree of fibrin cross-linking and hemolysis rate. After intravenous administration of HbPs to mice with controlled hemorrhages, blood flow recovery and maintenance of systemic oxygenation were observed. [ABSTRACT FROM AUTHOR]