Hemoglobin-loaded ZIF-8 nanoparticles equipped with PEGylated metal-phenolic network coatings: an oxygen carrier with antioxidant and stealth properties

Abstract

Hemoglobin-based oxygen carriers (HBOCs) offer a promising alternative to conventional blood transfusions in emergency scenarios. However, achieving optimal stability, functionality, and biocompatibility in HBOCs remains a significant challenge. In this study, we employed a HBOC formulation consisting of hemoglobin (Hb) encapsulated within zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (NPs). These NPs were subsequently coated with metal phenolic networks (MPNs) and polyethylene glycol (PEG) to impart antioxidant properties and enhance their stability and biocompatibility. Hb-loaded ZIF-8 NPs were synthesized using a rapid, environmentally friendly protocol and exhibited desirable properties, including an average size of approximately 150 nm, a negative surface charge (zeta potential of −14 mV), high encapsulation efficiency (approximately 65%), and substantial drug loading capacity (around 70%). The MPN coating significantly enhanced stability across various buffers and cell media and endowed the NPs with antioxidant properties. Meanwhile, the PEG layer conferred stealth properties, potentially extending circulation times in vivo. Furthermore, the NPs showed excellent biocompatibility in terms of cell viability and hemolysis rate studies. They also efficiently bound and released oxygen across multiple cycles, demonstrating preserved functionality. These attributes highlight the potential of our novel HBOC as an effective oxygen delivery system and position our formulation as a promising candidate for clinical application in critical care, providing a strategic alternative to traditional blood transfusions.