A cobalt-doped iron oxide nanozyme as a highly active peroxidase for renal tumor catalytic therapy

The Fe₃O₄ nanozyme, the first reported nanozyme with intrinsic peroxidase-like activity, has been successfully employed for various diagnostic applications. However, only a few studies have been reported on the therapeutic applications of the Fe₃O₄ nanozyme partly due to its low affinity to the substrate H₂O₂. Herein, we report a new strategy for improving the peroxidase-like activity and affinity of the Fe₃O₄ nanozyme to H₂O₂ to generate reactive oxygen species (ROS) for kidney tumor catalytic therapy. We showed that cobalt-doped Fe₃O₄ (Co@Fe₃O₄) nanozymes possessed stronger peroxidase activity and a 100-fold higher affinity to H₂O₂ than the Fe₃O₄ nanozymes. The lysosome localization properties of Co@Fe₃O₄ enable Co@Fe₃O₄ to catalyze the decomposition of H₂O₂ at ultralow doses for the generation of ROS bursts to effectively kill human renal tumor cells both in vitro and in vivo. Moreover, our study provides the first evidence that the Co@Fe₃O₄ nanozyme is a powerful nanozyme for the generation of ROS bursts upon the addition of H₂O₂ at ultralow doses, presenting a potential novel avenue for tumor nanozyme catalytic therapy.