Integrated design and application of metal–organic frameworks in ferroptosis-mediated cancer therapy

Cancer is the most malignant disease in the world, and there is an urgent need to explore new and efficient therapeutic approaches. Ferroptosis, a new form of cell death, is characterized by the accumulation of reactive oxygen species and lipid peroxide, which has broad application scenarios in antagonizing the resistance to traditional cell death and enhancing the eradication of tumor cells. However, the limited ROS in cancer cells and their inherent antioxidant substrates such as glutathione counteract ferroptosis. In addition, glutathione peroxidase 4 and ferroptosis suppressor 1 confer ferroptosis resistance. With the gradual advancement of ferroptosis research and the rise of emerging technologies such as nanomaterials, targeted drugs and therapeutics for tumor cell ferroptosis show great potential. Metal-organic frameworks (MOFs), with their porous structure and large surface area, are one of the most attractive multimodal therapeutic platforms available. Hence, this review summarizes the recent advances in the design and application of various MOFs for ferroptosis-mediated cancer therapy. Based on the molecular mechanisms of ferroptosis regulation and the pathways of MOF-mediated ferroptosis, we generalize the strategies of surface modifications to MOFs and highlight the combination of various MOF-based ferroptosis strategies with chemotherapy, photothermal therapy, photodynamic therapy, immunotherapy, and others. Moreover, we illustrate the current state of research on the link between ferroptosis and cuproptosis.