Metal–Organic Framework Nanocomposites in Conquering Hypoxia for Tumor Therapy

Abstract Hypoxia, as a distinctive feature of tumors, is closely related to tumor recurrence, metastasis, and treatment resistance. Metal–organic framework (MOF) exhibits an increasing number of advantages in cancer therapy owing to its porous structure, large specific surface area, and tunable function. The MOF nanocomposites constructed by adjusting components can effectively overcome tumor hypoxia and significantly enhance the anti‐tumor effect. In this review, the hypoxic characteristics of tumors and current strategies for constructing MOF nanocomposites that can overcome tumor hypoxia are summarized, including for delivering O 2 or endogenously generating O 2 to elevate intra‐tumor O 2 content; inhibiting HIF‐1 and its induced products to alleviate tumor hypoxia; reducing cellular aerobic respiration to decrease cellular O 2 consumption, and exacerbating hypoxia to improve the efficacy of hypoxia‐activated pre‐drugs. At the same time, the applications of MOF nanocomposites applied to overcome tumor hypoxia in different therapeutic methods at the present stage are described, and finally, the challenges and opportunities in further development of MOF nanocomposites are discussed.