While tumor hypoxia is recognized as a key barrier to effective chemo and radiation therapy of solid tumor malignancies, and an important biological mediator of more aggressive tumor phenotype and behavior for over 50 years, prior attempts to improve tumor oxygenation have relied on increasing the total amount of oxygen bound to each molecule of natural hemoglobin (e.g. through hyperbaric oxygen treatments), increasing the ease of release of oxygen from hemoglobin (through the introduction of exogenous allosteric small molecules), or increasing the total amount of oxygen in the body by injecting perfluorocarbon emulsions, or polymerized or pegylated compositions of natural human or bovine hemoglobin. The embodiments provide a novel approach of introducing into the vascular system agents that possess inherently higher-affinities for molecular oxygen that that of natural human hemoglobin, and coupling these agents with inert carriers that shield them from unwanted biological interactions within the body.
