Metal-Organic Framework Nanocomposites in Conquering Hypoxia for Tumor Therapy

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 O2 or endogenously generating O2 to elevate intra-tumor O2 content; inhibiting HIF-1 and its induced products to alleviate tumor hypoxia; reducing cellular aerobic respiration to decrease cellular O2 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. Hypoxia is closely related to tumor treatment resistance. Metal-organic framework (MOF) exhibits an increasing number of advantages in cancer therapy In this review, the hypoxic characteristics of tumors, current strategies for constructing MOF nanocomposites to overcome tumor hypoxia and the applications of MOF nanocomposites in different therapeutic methods are summarized. Finally, the challenges and opportunities in further development of MOF nanocomposites are discussed.image