In vitro and in vivo investigations of hemoglobin-loaded PEGylated ZIF-8 nanoparticles as oxygen carriers for emergency transfusion

Abstract

The limitations of traditional blood supply systems, particularly where ideal storage is unfeasible, challenge the efficacy of transfusion medicine, especially in emergencies and battlefield scenarios. This study investigates a novel hemoglobin-based oxygen carrier (HBOC) using a dual-coating approach with metal phenolic networks (MPNs) and polyethylene glycol (PEG). Utilizing zeolitic imidazolate framework-8 (ZIF-8) nanoparticles for their porosity and biocompatibility, the addition of MPN and PEG coatings enhances biocompatibility and stabilizes encapsulated hemoglobin (Hb). This reduces Hb release and minimizes interactions with the coagulation cascade, as evidenced by stable prothrombin and activated partial thromboplastin times. Complement activation studies showed slight increases in C5a levels, indicating low potential for severe immune reactions. In vivo evaluations demonstrated that both MPN-coated and PEGylated Hb-loaded ZIF-8 NPs have enhanced circulation times, with significantly longer half-lives than free Hb. However, PEGylation did not offer additional benefits over MPN coating alone, possibly due to suboptimal PEG density or shielding. Biodistribution studies indicated similar accumulation patterns in the liver and kidneys for both NP types, suggesting common clearance pathways. These findings suggest our PEGylated Hb-loaded ZIF-8 NPs as promising alternatives to traditional transfusions. Future research will assess their efficacy in resuscitation from hemorrhagic shock to validate their clinical application.