Abstract: As an essential substance for maintaining life activities and metabolic processes, oxygen plays an irreplaceable role in regulating physiological homeostasis and treating disease. The clinical field currently faces severe challenges such as blood supply shortages and transfusion-related infection risks, prompting researchers to develop safe and efficient artificial oxygen carriers (AOCs) as red blood cell substitutes. Hemoglobin-based oxygen carriers (HBOCs) have gained significant attention in this context due to their oxygen-carrying capacity being similar to that of natural red blood cells. This makes them a key area of research in the development of alternative transfusion therapies. However, traditional HBOCs present challenges for clinical use due to their vasoconstrictive activity, oxidative stress toxicity, and short circulatory half-life. Advances in nanotechnology have enabled researchers to develop a new generation of HBOC nanomaterial systems using innovative strategies such as haemoglobin nano-encapsulation, surface functionalisation modification, and biomolecular conjugation. These novel carriers significantly overcome the limitations of traditional HBOCs and have promising applications in fields such as trauma emergency care, treatment of ischaemic diseases, and tumour oxygenation regulation. This paper provides a comprehensive review of research progress on HBOCs and nanomaterial-based HBOCs, analysing their advantages and challenges for future clinical applications.

Key words: Artificial oxygen carriers, Hemoglobin-based oxygen carriers, Nanomaterials, Oxygen transport, Red blood cell substitutes