HBOCs in Cancer
One challenge in treating solid tumors is low oxygen in the core of the tumor. Under these conditions, the cancer cells become resistant to many of the chemotherapies used to treat these conditions. In fact, these chemotherapies have a response rate of only 20%. We urgently need new methods to increase the effectiveness of these chemotherapies.
In our lab we have previously developed a way to produce a bio-engineered blood substitute that is capable of delivering oxygen to the tumor. (especially when the oxygen content is low.) With this knowledge we are developing new ways to make these materials more effective using new synthesis techniques guided with complex computational models.Specifically, polymerized human hemoglobin (PolyhHb) can be transfused into the systemic circulation to increase solid tumor oxygenation, and improve chemotherapeutic outcomes.
By locking PolyhHb in the relaxed (R) quaternary state, oxygen (O2) offloading at low O2 tensions (<20 mm Hg) may be increased, while O2 offloading at high O2 tensions (>20 mm Hg) is facilitated with tense (T) state PolyhHb. Therefore, R-state PolyhHb may deliver significantly more O2 to hypoxic tissues.
Belcher, D. A.; Ju, J. A.; Baek, J. H.; Yalamanoglu, A.; Buehler, P. W.; Gilkes, D. M.; Palmer, A. F. The Quaternary State of Polymerized Human Hemoglobin Regulates Oxygenation of Breast Cancer Solid Tumors: A Theoretical and Experimental Study. PLoS One 2018, 13 (2). https://doi.org/10.1371/journal.pone.0191275.
Belcher, D. A.; Banerjee, U.; Baehr, C. M.; Richardson, K. E.; Cabrales, P.; Berthiaume, F.; Palmer, A. F. Mixtures of Tense and Relaxed State Polymerized Human Hemoglobin Regulate Oxygen Affinity and Tissue Construct Oxygenation. PLoS One 2017, 12 (10), e0185988. https://doi.org/10.1371/journal.pone.0185988.