Nanoenabled Tumor Oxygenation Strategies for Overcoming Hypoxia-Associated Immunosuppression

Cancer immunotherapy, which initiates or strengthens innate immune responses to attack cancer cells, has shown great promise in cancer treatment. However, low immune response impacted by immunosuppressive tumor microenvironment (TME) remains a key challenge, which has been found related to tumor hypoxia. Recently, nanomaterial systems are proving to be excellent platforms for tumor oxygenation, which can reverse hypoxia-associated immunosuppression, strengthen the systemic antitumor immune responses, and thus afford a striking abscopal effect to clear metastatic cancer cells. In this review, we would like to survey recent progress in utilizing nanomaterials for tumor oxygenation through approaches such as in situ O₂ generation, O₂ delivery, tumor vasculature normalization, and mitochondrial-respiration inhibition. Their effects on tumor hypoxia-associated immunosuppression are highlighted. We also discuss the ongoing challenges and how to further improve the clinical prospect of cancer immunotherapy.