Nanobiotechnological basis of an oxygen carrier with enhanced carbonic anhydrase for CO2 transport and enhanced catalase and superoxide dismutase for antioxidant function

Abstract

This is a mini review on the biotechnological aspects of the most extensively developed hemoglobin-based oxygen carriers The emphasis is on the most recent Polyhemoglobin-catalase-superoxide dismutase-carbonic anhydrase (PolyHb-CAT-SOD-CA), which is a nanobiotechnological complex that is being investigated and scaled up with the potential for clinical use as nanobiotherapeutics. Hemoglobin, a tetramer, is an excellent oxygen carrier. However, in the body it is converted into toxic dimers. Diacid or glutaraldehyde can crosslink hemoglobin into polyhemoglobin (PolyHb) and prevent its breakdown into toxic dimers. This has been developed and tested in clinical trials. A bovine polyhemoglobin has been approved for routine clinical use for surgical procedures in South Africa and Russia. Clinical trials with human PolyHb in hemorrhagic shock were effective but with a very slight increase in non-fatal myocardial ischemia. This could be due to a number of reasons. For those conditions with ischemia-reperfusion, one would need an oxygen carrier with antioxidant properties. One approach to remedy this is with prepared polyhemoglobin-catalase-superoxide dismutase (PolyHb-CAT-SOD). Another reason is an increase in intracellular pCO2. We therefore added an enhanced level of carbonic anhydrase to prepare a PolyHb-CAT-SOD-CA. The result is an oxygen carrier with enhanced Carbonic Anhydrase for CO2 transport and enhanced Catalase and Superoxide Dismutase for antioxidant functions. Detailed efficacy and safety studies have led to the industrial scale up towards clinical trial. In the meantime, oxygen carriers are being investigated around the world for use in ex vivo biotechnological fluid for organ preservation for transplantation, with one already approved in France.

How Nitric Oxide Hindered the Search for Hemoglobin-Based Oxygen Carriers as Human Blood Substitutes

“…Although the issues related to NO scavenging by microencapsulated Hb may appear still controversial, this technique enables the incorporation of other proteins with various roles into the macrovesicles, for example carbonic anhydrase to enhance carbon dioxide transport and catalase/superoxide dismutase to enhance the antioxidant function [190]. This formulation proved efficient in a rat hemorrhagic-shock model with a two-thirds bloodvolume loss and 90 min of sustained shock, to enable faster recovery of the heart from ischemia, better histological findings in the post-ischemic intestine, and more favorable tests for anaphylactic reactions [191].…”

Nanomaterial-related hemoglobin-based oxygen carriers, with emphasis on liposome and nano-capsules, for biomedical applications: current status and future perspectives

“…For instance, preventing the dissociation of hemoglobin tetramer and reducing nephrotoxicity [ 53 , 54 ] by optimizing the molecular weight of the polymer [ 55 ]. Hb oxidation is reduced by co-cross-linking Hb with internal biological enzymes such as superoxide dismutase (SOD) and catalase (CAT) [ 56 – 58 ]. While these technical strategies have reduced the safety concerns of HBOCs to extent; they are still in the preclinical research stage.…”