Haemoglobin-loaded metal organic framework-based nanoparticles camouflaged with a red blood cell membrane as potential oxygen delivery systems

Transfusion of donor red blood cells (RBCs) is a crucial methodology required for the treatment of acute trauma and anaemia or for surgical procedures. Due to the many limitations of donor blood, numerous strategies have been explored to develop haemoglobin (Hb)-based oxygen carriers to be used as oxygen delivery systems. However, since free Hb suffers from a lack of stability and short circulation times in blood, an encapsulation platform is needed. Herein, we entrap Hb within a type of metal organic framework (MOF)-based nanoparticle (MOF-NP). By doing so, Hb is protected from misfolding and denaturation, which is a crucial aspect to preserve its excellent oxygen binding and releasing properties. Furthermore, the porous structure of MOF-NPs allows for the diffusion of small molecules (i.e., oxygen) in and out of the system. Our results show that the Hb-loaded MOF-NPs (MOF^Hb-NPs) are monodisperse and show a small hydrodynamic diameter of ∼220 nm. Importantly, the structure and functionality of the encapsulated Hb are well preserved. To achieve long circulation in the bloodstream, we functionalized MOF^Hb-NPs with naturally derived RBC membranes and compared the stealth properties of the membrane-coated MOF^Hb-NPs with our previously reported PEGylation strategy. Protein adsorption and cell uptake studies demonstrate that both coatings are able to significantly decrease the adsorption of proteins and also diminish their uptake by macrophages and endothelial cells. Furthermore, both types of coatings endow MOF^Hb-NPs with good biocompatibility and oxygen binding and releasing properties. Overall, this study presents a novel oxygen carrier system which might find applications as a blood surrogate.