Evaluating Chemo-Sensitizing Potential of Oxygen Delivery Facilitated By Transfused Polymerized Hemoglobins on Vascularized Solid Tumors

A major constraint in chemo-and radio-therapeutic cancer treatment is inadequate oxygenation of solid tumors. Consequently, alleviating hypoxia in solid tumors is considered a promising target for improving the efficacy of anti-cancer therapeutics such as chemotherapy. Our group has synthesized variable molecular weight (MW) Polymerized human hemoglobin (PolyhHb) with low (T-state) and high (R-state) oxygen (O₂) affinities for use as RBC substitutes. These O₂ carriers can be transfused to increase solid tumor oxygenation and improve the efficacy of anti-cancer therapeutics. In this study, we analyzed the biophysical properties of the synthesized PolyhHbs. Three-dimensional computational models of blood flow and O₂ transport in the tumor micro-environment were used to examine how dosage and type of PolyhHb impacted tumor O₂ delivery. To compliment this study, an animal study was performed by periodically delivering PolyhHb in the T- and R-state. Decreases in the apparent viscosity resulting from PolyhHb exchange transfusion may result in significant changes in flow distributions throughout the tumor micro-circulatory network. The difference in wall shear stress implies that PolyhHb may have a more significant effect on capillary beds. The increased O₂ flux and decreased pO₂ drop per unit length indicates that both PolyhHbs are suited to deliver O₂ under hypoxic conditions. Both T- and R-state PolyhHb exchange transfusion may lead to elevated O₂ delivery at low pO_2,in. In the experimental mouse model, HBOC transfusion led to decreased angiogenesis, tumor growth, and hypoxic gene expression.