Nanozymes for Advanced Hemoglobin-Based Oxygen Carriers: Applications in Blood Substitution, Wound Healing, Antitumor...

Oxygen delivery and reactive oxygen species regulation are tightly linked in physiology, with red blood cells serving both as oxygen transporters and as a key antioxidant barrier. This dual function has motivated decades of research into hemoglobin (Hb)-based oxygen carriers (HBOCs), yet conventional designs remain susceptible to oxidative damage and lack the redox machinery of erythrocytes. In parallel, nanozymes-nanomaterials with enzyme-mimetic catalytic activities-have emerged as powerful tools in redox medicine. Their integration with HBOCs has created a new class of self-protecting, multifunctional, and stimuli-responsive oxygen therapeutics. This review summarizes the foundations and biomedical potential of nanozyme-integrated HBOCs and Hb-derived nanozymes. We outline how metal, carbon, and metal-organic framework nanozymes replicate key antioxidant functions, including superoxide dismutase-, catalase-, and peroxidase-like activity. Embedding such nanozymes into HBOCs imparts intrinsic oxidative protection and additional capabilities such as carbonic anhydrase-like catalysis, transforming passive oxygen carriers into intelligent blood substitutes. We then highlight applications beyond transfusion, including wound healing, where photothermal nanozyme-HBOC hybrids enable light-controlled oxygen release and antibacterial action, and cancer therapy, where catalytic HBOCs alleviate tumor hypoxia and enhance radiotherapy, photothermal therapy, and photodynamic therapy. Finally, we discuss Hb-derived and erythrocyte-templated nanozymes for biosensing, radioprotection, and infection control.