Restoring normoxia in hypoxic cancer cells via hemoglobin-loaded MOF nanoparticles

Abstract

Hypoxia, a condition characterized by low oxygen (O₂) levels, poses significant challenges in medical and therapeutic contexts, especially in tumor environments where it promotes resistance to chemotherapy and radiotherapy. In this study, we present the fabrication and characterization of hemoglobin (Hb)-loaded zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (NPs) coated with human serum albumin (HSA) (termed as Hb@ZIF-8/HSA NPs) as potential O₂ carriers for hypoxia alleviation. These NPs demonstrated high Hb content and encapsulation efficiency, O₂-controlled release, and biocompatibility. Their functionality was evaluated using an optimized in vitro hypoxia model with SH-SY5Y cells. Our results show that Hb@ZIF-8/HSA NPs effectively downregulate hypoxia-inducible factor 1α (HIF-1α) expression in a concentration-dependent manner and fully restore normoxic conditions under hypoxic stress at a dose of only 0.5 mg mL^-1. These findings underscore the potential of Hb@ZIF-8/HSA NPs as therapeutic tools for hypoxia-related conditions, with promising applications in enhancing cancer therapy outcomes.

Keywords: Cancer therapy; Hemoglobin; Hypoxia; Hypoxia-inducible factor 1α; Metal-organic frameworks; Oxygen carriers.