Optimization and Investigation of Hemoglobin-Loaded ZIF-90 Metal–Organic Framework Nanoparticles as Artificial Oxygen Carriers

Blood transfusions are vital, yet limited shelf-life and storage conditions of red blood cells (RBCs) hinder their use in emergencies. Hemoglobin-based oxygen carriers (HBOCs) aim to address these challenges, but previous versions faced clinical setbacks due to safety concerns related to hemoglobin (Hb) extravasation. ZIF-90, a novel metal–organic framework variant where imidazole-2-carboxaldehyde (2-ICA) is bridged to Zn²⁺ ions, is explored. Optimizing Zn²⁺:2-ICA ratios and Hb concentrations, Hb-loaded ZIF-90 nanoparticles (NPs) are synthesized in one-step and under mild synthesis conditions. These NPs achieve a 25.1% yield, 7.0 mg mL⁻¹ Hb concentration, 70.3% encapsulation efficiency (EE), and 96.4% drug loading. They exhibit a left-shifted oxygen dissociation curve with p50 of ≈8 mmHg, indicating enhanced oxygen release at lower partial oxygen pressures as compared to native RBCs. This feature makes Hb-loaded ZIF-90 NPs suitable for certain medical applications including ischemia-reperfusion injury management. Furthermore, the impact of two prominent capping agents: polyvinylpyrrolidone and polyethylene glycol (PEG) is assessed. PEG improves 2-ICA incorporation and stabilizes the ZIF-90 crystalline phase, albeit with reduced yield, Hb content, and EE. The findings underscore the potential of Hb-loaded ZIF-90 NPs as next-generation HBOCs, offering enhanced uniformity, high Hb content, and efficient oxygen binding and release properties for medical applications.