Breaking hypoxic barrier: Oxygen-supplied nanomaterials for enhanced T cell-mediated tumor immunotherapy

作者：Shuo Xiang, Hui Zhan, Jiaming Zhang, Xin Li, Xiaoji Lin, Wenjie Sun · 发表于：International Journal of Pharmaceutics X · 年份：2025 · DOI：10.1016/j.ijpx.2025.100400 · 被引用次数：13 · 研究领域：Adenosine and Purinergic Signaling、Nanoplatforms for cancer theranostics、Immune cells in cancer

Hypoxia in the tumor microenvironment (TME) is a critical barrier to effective cancer immunotherapy, as it suppresses T cell infiltration and response while fostering immune evasion. Oxygen-supplied nanomaterials (OSNs) have recently emerged as promising tools to alleviate hypoxia, modulate the TME, and enhance the efficacy of immunotherapies. This review explores the synergistic interplay between OSNs and T lymphocytes in overcoming hypoxia-driven immune suppression. We discuss the mechanisms by which hypoxia limits T cell functionality, infiltration, and cytotoxicity, and highlight how nanomaterials restore oxygenation, boost immune activation, and improve chemokine-mediated T cell recruitment. Key advances in nanotechnology, including perfluorocarbon-based systems and catalytic nanoparticles, are evaluated for their ability to improve anti-tumor immunity and synergize with immune checkpoint inhibitors and chimeric antigen receptor-T cell therapies. Finally, we address the challenges of nanomaterial delivery, safety, and clinical translation, emphasizing opportunities for personalized strategies. OSNs offer transformative potential to enhance T cell-mediated anti-tumor responses, advancing immunotherapy's frontier.