title: Hemoglobin-based oxygen carrier enhanced tumor oxygenation: a novel strategy for cancer therapy.
abstract: A tumor's low oxygen tension is a major obstacle to current chemo- and radio-therapies. By increasing oxygen transport to hypoxic tumor regions it is possible to make tumors more susceptible to current cancer treatment strategies. This article theoretically investigates the possibility of supplementing human blood with hemoglobin-based oxygen carriers (HBOCs) in an attempt to target oxygen delivery specifically to the low oxygen tension regions present in tumors. In this work, we develop a mathematical model that describes oxygen transport in a cylindrical annulus of cancerous tissue fed by a single cylindrical capillary. The oxygen transport model was used to evaluate mixtures of red blood cells and six types of HBOCs that consisted of two polymerized hemoglobins, two liposome-encapsulated hemoglobins, and two hydrogel-encapsulated hemoglobins. These HBOCs span a wide range of oxygen affinities (P(50)s) ranging from 5 to 54 mm Hg to study the effect of P(50) on the ability to target oxygen delivery to hypoxic regions of a tumor and hence improve tumor oxygenation. The results of these simulations indicate that each HBOC has an effective pO(2) range in which it unloads the most oxygen, which is dependent on the HBOC's P(50). Although it would seem that the HBOC with the lowest P(50) (5 mm Hg) should be the best option for O(2) delivery to hypoxic tumors, our results indicate that when this is the case, the lowest P(50) HBOC yielded insufficient O(2) delivery to normoxic tissues (inlet pO(2) approximately 95 mm Hg). Because HBOCs would be transfused into a patient's blood stream before initiating a particular cancer therapy, sufficient oxygen must be delivered to both normoxic and cancerous tissues to maintain normal tissue functions when oxygenating the tumor. Human blood supplemented with a hydrogel-encapsulated Hb with a P(50) of 10 mm Hg was found to deliver sufficient oxygen to normoxic tissue while increasing oxygen delivery to hypoxic regions of tumorgenic tissue. Taken together, this work represents a novel strategy for enhancing the efficacy of existing cancer therapies.
authors.affiliation: Dept. of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, IN 46556, USA.
authors.forename: Sharon I
authors.initials: SI
authors.lastname: Gundersen
authors.forename: Andre F
authors.initials: AF
authors.lastname: Palmer
mesh_terms: D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use*; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism*; D010101:Oxygen Consumption; D023822:Tissue Engineering
chemical_list: D006454:Hemoglobins; C402601:hemoglobin glutamer-200; D010100:Oxygen