Metal-organic framework-based oxygen carriers with antioxidant protection as a result of a polydopamine coating.

Abstract

Rapid haemorrhage control to restore tissue oxygenation is essential in order to improve survival following traumatic injury. To this end, the current clinical standard relies on the timely administration of donor blood. However, limited availability and portability, special storage requirements, the need for blood type matching and risks of disease transmission result in severe logistical challenges, impeding the use of donor blood in pre-hospital scenarios. Therefore, great effort has been devoted to the development of haemoglobin (Hb)-based oxygen carriers (HBOCs), which could be used as a "bridge" to maintain tissue oxygenation until hospital admission. HBOCs hold the potential to diminish the deleterious effects of acute bleeding and associated mortality rates. We recently presented a novel HBOC, consisting of Hb-loaded metal organic framework (MOF)-based nanoparticles (NPs) (MOFHb-NPs), and demonstrated its ability to reversibly bind and release oxygen. However, a long standing challenge when developing HBOCs is that, over time, Hb oxidizes to non-functional methaemoglobin (metHb). Herein, we address this challenge by modifying the surface of the as-prepared MOFHb-NPs with an antioxidant polydopamine (PDA) coating. The conditions promoting the greatest PDA deposition are first optimized. Next, the ability of the resulting PDA-coated MOFHb-NPs to scavenge important reactive oxygen species is demonstrated both in a test tube and in the presence of two relevant cell lines (i.e., macrophages and endothelial cells). Importantly, this antioxidant protection translates into minimal metHb conversion.