Iron-based nanozymes induced ferroptosis for tumor therapy

Iron-based nanozymes are an emerging class of nanomaterials demonstrating significant potential in tumor therapy by inducing ferroptosis—a regulated form of cell death marked by iron-mediated lipid peroxidation (LPO). These nanozymes exhibit unique enzymatic activities, including peroxidase, oxidase, and glutathione oxidase-like functions, enabling them to generate reactive oxygen species (ROS) and disrupt tumor microenvironment homeostasis. Leveraging Fenton chemistry, iron-based nanozymes amplify oxidative stress within tumor cells, thereby overcoming therapeutic challenges such as drug resistance and nonspecific toxicity. Despite significant advancements, the precise mechanisms by which iron-based nanozymes influence ferroptosis and their therapeutic efficacy remain underexplored. This review systematically categorizes these iron-based nanozymes, including iron oxides, single-atom enzymes, and metal-organic frameworks. We further elucidate their mechanisms in enhancing ferroptosis, focusing on their structural attributes, ROS generation pathways, and their enzymatic activities. Additionally, we summarized their biochemical applications alongside challenges in biosafety, nanozyme specificity, and advanced design and analysis approaches essential for maximizing their therapeutic efficacy.