Vanadium Single-Atom Nanozyme Boosts Cuproptosis/Ferroptosis/Apoptosis Combined with Photothermal-Enhanced Tumor Therapy through Dual Catalytic Activity

Nanocatalysts hold significant promise in tumor therapy by facilitating the production of reactive oxygen species (ROS) within the tumor microenvironment (TME). Among these, single-atom nanozymes (SAzymes) stand out due to their atomically dispersed active sites, offering a viable alternative to natural enzymes. SAzyme can simulate the catalytic mechanisms of natural enzymes, such as peroxidase and catalase, achieving highly efficient biocatalytic effects. Moreover, they can maintain high catalytic activity and structural stability under extreme conditions. However, the application of SAzymes in anticancer treatments is still in its initial stages, necessitating further research and development. In this study, we have synthesized a single-atom catalytic enzymes with V₂O₅ coordination (vanadium-based single-atom catalysts, V-SAC) utilizing the electrospinning technique to enhance tumor suppression. The V-SAC demonstrates notable dual enzymatic activities, mimicking both peroxidase and glutathione peroxidase functions. It catalyzes the conversion of endogenous H₂O₂ to ·OH within the acidic tumor microenvironment, while simultaneously depleting glutathione (GSH). Significantly, V-SAC induces cuproptosis/ferroptosis/apoptosis, which further augments the efficacy of tumor treatment. Additionally, the exceptional photothermal properties of V-SAC enable photothermal therapy (PTT) for tumors. In vivo experiments reveal that V-SAC exhibits excellent antitumor capabilities coupled with high safety, underscoring its substantial potential for clinical applications in cancer treatment. These findings highlight the development of high-performance, biological safety single-atom catalysts for biomedical applications in tumor therapy.