Nanozyme-enhanced ferroptosis for cancer treatment

Ferroptosis is a programmed, iron-dependent, oxidative cell death that was discovered recently. It is usually accompanied by iron accumulation and lipid peroxidation during the cell death process. Ferroptosis-inducing factors affect glutathione (GSH) peroxidase directly or indirectly, leading to a decrease in antioxidant capacity and accumulation of lipid reactive oxygen species (ROS). Ferroptosis has garnered much interest in the field of cancer treatment. However, the therapeutic efficacy through the ferroptosis pathway by directly increasing the levels of iron ions at cancer lesion is not ideal due to the inefficient enrichment of iron ions at the lesion site, the uncontrolled Fenton reaction and a single apoptotic pathway. Nanozymes are nanomaterials that can catalyse enzyme substrates into products following enzyme kinetics under physiological conditions. Nanozymes offer advantages such as enhanced stability, simplified preparation, and cost-effectiveness compared to natural enzymes. Notably, nanozymes can serve as self-activated cascade reagents, elevating the therapeutic efficacy of cancer through the ferroptosis pathway by effectively generating reactive ROS and depleting GSH. Furthermore, nanozymes can induce ferroptosis and synergize with other approaches such as photothermal therapy (PTT), photodynamic therapy (PDT), and immunotherapy. Presented in this review are the definition, structure, classification, and features of nanozymes, the fundamental mechanisms of ferroptosis in cancer cells, and the combined strategies employed to combat cancer by leveraging nanozymes to induce or enhance ferroptosis. Nanozymes could mimic the catalytic activity of natural enzymes, then stimulate the Fenton reaction for reactive oxygen species overproduction and lipid peroxidation, ultimately induce ferroptosis to exert anticancer effects.