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Emerging Nanoplatforms are Effective Against Tumor Hypoxia

Yu Z, Shang Y, He W, Xia X, Zhou L

International journal of nanomedicine, 2026

Abstract

Hypoxia is a characteristic feature of the solid tumor microenvironment and serves as a pivotal factor in tumor progression, metastasis, and therapeutic resistance. It has long been recognized as a significant barrier to advancing cancer therapy. Although traditional oxygen supplementation strategies can partially enhance local oxygen levels, their effectiveness is limited by the spatiotemporal heterogeneity of tumor tissues, low delivery efficiency, and biosafety concerns, making them inadequate for the precise oxygen regulation required by the complex tumor microenvironment. In recent years, nanotechnology-based platforms designed to alleviate hypoxia have emerged as innovative approaches for remodeling the tumor microenvironment and enhancing multimodal synergistic therapies. These platforms operate through three primary strategies: exogenous oxygen delivery, endogenous oxygen generation, and metabolic oxygen conservation. This review systematically elucidates the underlying mechanisms of tumor hypoxia, summarizes the design principles and recent advancements of related nanomedicines, and discusses the potential and challenges of these platforms in multimodal combination therapies. The study aims to furnish a comprehensive reference for the design of hypoxia-alleviating nanoplatforms and the optimization of synergistic therapeutic strategies, with the objective of providing novel insights and prospects for the development of nanomaterials in this domain.

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