The Molecular Size of Bioengineered Oxygen Carriers Determines Tissue Oxygenation in a Hypercholesterolemia Guinea Pig Model of Hemorrhagic Shock and Resuscitation.

Polymerized human hemoglobin (PolyhHb) has shown promise in preclinical hemorrhagic shock settings. Different synthetic and purification schemes can control the size of PolyhHbs, yet research is lacking on the impact of polymerized hemoglobin size on tissue oxygenation following hemorrhage and resuscitation in specialized animal models that challenge their resuscitative capabilities. Pre-existing conditions that compromise the vasculature and end organs, such as the liver, may limit the effectiveness of resuscitation and exacerbate the toxicity of these molecules, which is an important but minimally explored therapeutic dimension. In this study, we compared the effective oxygen delivery of intermediate molecular weight PolyhHb (PolyhHb-B3; 500-750 kDa) to high molecular weight PolyhHb (PolyhHb-B4; 750 kDa-0.2 µm) for resuscitative effectiveness in guinea pig models subjected to hemorrhagic shock. We evaluated how the size of PolyhHb impacts hemodynamics and tissue oxygenation in normal guinea pigs and guinea pigs on an atherogenic diet. We observed that while PolyhHb-B3 and -B4 equivalently restore hemodynamic parameters of normal-dieted guinea pigs, high-fat-dieted guinea pigs resuscitated with PolyhHb-B4 have lower mean arterial pressures, impaired tissue oxygenation, and higher plasma lactate levels than those receiving PolyhHb-B3. We characterized the plasma of these animals following resuscitation and found that despite similar oxygen delivery kinetics, circulating PolyhHb-B3 and -B4 demonstrated a size-dependent increase in the plasma viscosity, consistent with impaired perfusion in the PolyhHb-B4 transfusion group. We conclude that intermediate-sized PolyhHbs (such as -B3) are ideal for further research given the effective resuscitation of hemorrhagic shock based on tissue oxygenation in hypercholesterolemic guinea pigs.

Strategies of Alleviating Tumor Hypoxia and Enhancing Tumor Therapeutic Effect by Macromolecular Nanomaterials.

Hypoxia as one of the most prominent features in tumors, has presented negative effects on tumor therapies including photodynamic therapy, radiotherapy, and chemotherapies, leading to the tumor regeneration and metastasis. Recently, nanomedicines have been proposed to handle the hypoxia dilemma. Some nanomedicines alleviated hypoxia to enhance the therapeutic effect, others used hypoxia-sensitive substances to treat tumor. Among them, macromolecular nanomaterials-based nanomedicine has attracted increased research interest. However, the complicated tumor microenvironment disturbs the practical application of macromolecular nanomaterials to deal with hypoxia. This review highlights the influence of hypoxia on tumor therapy and some new strategies of using macromolecular nanomaterials to overcome hypoxia for effective tumor therapy.

Perfluorocarbon-Loaded Hollow Bi2Se3 Nanoparticles for Timely Supply of Oxygen under Near-Infrared Light to Enhance the Radiotherapy of Cancer.

Hollow Bi2 Se3 nanoparticles prepared by a cation exchange method are loaded with perfluorocarbon as an oxygen carrier. With these nanoparticles, a promising concept is demonstrated to enhance radiotherapy by not only using their X-ray-absorbing ability to locally concentrate radiation energy in the tumor, but also employing near-infrared light to trigger burst release of oxygen from the nanoparticles to overcome hypoxia-associated radio-resistance.