Current status and prospects of MOFs loaded with HO-related substances for ferroptosis therapy.

Ferroptosis is a programmed cell death mechanism characterized by the accumulation of iron (Fe)-dependent lipid peroxides within cells. Ferroptosis holds excellent promise in tumor therapy. Metal-organic frameworks (MOFs) offer unique advantages in tumor ferroptosis treatment due to their high porosity, excellent stability, high biocompatibility, and targeting capabilities. Inducing ferroptosis in tumor cells primarily involves the production of reactive oxygen species (ROS), like hydroxyl radicals (˙OH), through iron-mediated Fenton reactions. However, the intrinsic HO levels in tumor cells are often insufficient to sustain prolonged consumption, limiting therapeutic efficacy if ˙OH production is inadequate. Therefore, catalyzing or supplementing the intracellular HO levels in tumor cells is essential for inducing ferroptosis by nanoscale metal-organic frameworks. This article reviews the biological characteristics and molecular mechanisms of ferroptosis, introduces HO-related substances, and reviews MOF-based nanoscale strategies for enhancing intracellular HO levels in tumor cells. Finally, the challenges and prospects of this approach are discussed, aiming to provide insights into improving the effectiveness of ferroptosis induced by MOFs.