Abstract

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.

Highlights

  • Nanozymes are a class of nanomaterials with intrinsic enzymelike activities.[1,2,3] Over the last decade, a wide variety of nanomaterials have been reported to possess natural enzyme-like activities.[1,2,3,4,5] The biochemical reactions catalyzed by these types of nanozymes exhibit similar enzymatic kinetics as in the case of natural enzymes

  • This study provides a promising strategy to enhance the peroxidase-like activity of the Fe3O4 nanozyme and achieves the purpose of Fe3O4 nanozyme based-renal tumor catalytic therapy

  • The synthesized Co@Fe3O4 nanozymes contained Fe and Co with the ratio of approximately 2 : 1; this con rmed that Co was successfully doped into the Fe3O4 nanozymes by the simple solvothermal method

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Summary

Introduction

Nanozymes are a class of nanomaterials with intrinsic enzymelike activities.[1,2,3] Over the last decade, a wide variety of nanomaterials have been reported to possess natural enzyme-like activities.[1,2,3,4,5] The biochemical reactions catalyzed by these types of nanozymes exhibit similar enzymatic kinetics as in the case of natural enzymes. Nanozymes exhibit comparable enzymatic activity but with much higher stability and lower cost as compared to natural enzymes. Their activities are tunable, and they can be integrated with nanosystems to achieve multifunctionality;[6,7] nanozymes possess signi cant potential for a wide range of applications in biomedicine such as in immunoassays, biosensors, and antibacterial and antibio lm agents.[4,8,9]. As a classical magnetic nanomaterial, iron oxide (Fe3O4) nanoparticles are the rst reported nanozyme with intrinsic peroxidase-like activity.[10,11] Fe3O4 nanozymes with intrinsic magnetic properties have been extensively used for biological applications including magnetic resonance imaging, magnetic drug delivery, magnetic hyperthermia and magnetic separation.[12,13,14] Based on its newly discovered catalytic properties, the Fe3O4 nanozyme can act as a multifunctional enzyme mimetic for versatile biomedical applications.[12]

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