Metal-organic frameworks-mediated reactive oxygen species modulation in the tumor microenvironment of digestive system malignancies: latest advances

Digestive system malignancies, such as gastric cancer (GC), colorectal cancer (CRC), and hepatocellular carcinoma (HCC), have become a major global challenge in cancer therapy. These tumors are characterized by high morbidity, strong metastatic potential, and significant chemoresistance, thus posing a severe threat to human digestive health. One of the primary mechanisms underlying the malignant progression of tumors and the development of drug-resistant phenotypes is the imbalance of redox homeostasis in the tumor microenvironment (TME). Its dysregulation is strongly associated with the increased proliferation and invasive potential of tumor cells. As key regulatory molecules in the redox network of the TME, reactive oxygen species (ROS) render precise modulation of their levels a promising strategy for cancer therapy. This approach can not only effectively induce programmed cell death in tumor cells but also reverse the immunosuppressive state of the TME, thus offering novel therapeutic targets for anti-tumor treatment. Metal-organic frameworks (MOFs) are closely associated with metal-based nanomaterials, acting as their excellent precursors and enabling precise modulation of their structures and properties through hybridization. The demand for the precise regulation of ROS in the TME of digestive system malignancies is perfectly met by MOFs, which have emerged as a highly promising nanoplatform for this research field. MOFs have unique advantages such as precisely designable architectures, abundant metallic catalytic active sites, TME-responsive degradation, and high drug loading capacity. This review elucidates the mechanisms underlying MOF-mediated ROS modulation in the TME and highlights its applications in various digestive system malignancies.