Metal-Organic Framework-Based Oxygen Carriers with Antioxidant Activity Resulting from the Incorporation of Gold-Based Nanozymes

Abstract Blood transfusions are a life-saving procedure since they can preserve the body’s oxygen levels in patients suffering from acute trauma, undergoing surgery, receiving chemotherapy or affected by severe blood disorders. Due to the central role of haemoglobin (Hb) in oxygen transport, the so-called Hb-based oxygen carriers (HBOCs) are currently being developed for situations where donor blood is not available. In this context, an important challenge to be addressed is the oxidation of Hb into methaemoglobin (metHb) which is unable to bind and release oxygen. Since within red blood cells, this process is prevented by a set of protective enzymes such as superoxide dismutase and catalase, several research groups have considered incorporating these enzymes to create HBOCs with antioxidant properties. However, the use of biological enzymes has important limitations related to their high cost, potential immunogenicity or low stability in vivo. Thus, nanomaterials with enzyme-like properties (i.e., nanozymes (NZs)) have emerged as a promising alternative. In this work, we evaluate the antioxidant properties of gold (Au)-based NZs following incorporation within a type of HBOC previously reported by our group (i.e., Hb-loaded metal organic framework (MOF)-based nanocarriers (NCs)). We first prepare Au-loaded Au@MOF-NCs and demonstrate their ability to catalytically deplete two prominent reactive oxygen species (ROS) (i.e., hydrogen peroxide and superoxide radical) which exacerbate Hb’s autoxidation. Furthermore, these catalytic properties are retained over several cycles. Following loading with Hb, we show how the ROS-scavenging properties resulting from the Au-based NZs, translate into a decrease in metHb content. All in all, these results highlight the potential of NZs to create novel HBOCs with antioxidant protection which may find applications as a blood substitute in the future.