Atomic‐Level High‐Entropy Nanozymes Enable Remarkable Endogenous Targeted Catalysis and Enhancing Tumor Photothermal Therapy

Nanozymes hold great potential in protecting human health. However, constructing new and efficient nanozymes is a significant challenge. Developing atomic-level nanozymes is a promising approach. Despite their potential, atomic-level high-entropy nanozymes have not been reported due to thermodynamic instability. Therefore, developing atomic-level high-entropy nanozymes are of great significance. What's more, further exploring their biomedical applications can open up new horizons for nanozymology. Here, the atomic-level high-entropy nanozyme system capable of remarkable endogenous targeted catalysis and enhancing tumor photothermal therapy is successfully constructed. The system is prepared by reduction-diffusion and grafting methods. The RuRhPtIrMo sub-nanometer high-entropy nanozyme (snHEAzyme) with about 8-10 atoms thickness is first prepared. Then, they are grafted by targeting agent DSPE-PEG2000-cRGD and imaging agent Cy7 to obtain the snHEAzyme@DSPE-PEG2000-cRGD@Cy7 nanozyme system. The synthesized snHEAzyme@DSPE-PEG2000-cRGD@Cy7 system exhibits excellent peroxidase-like activity and high absorbance in the near-infrared (NIR) range. Under NIR irradiation, the nanozyme shows efficient photothermal conversion and reactive oxygen species generation effects. In vitro and in vivo experiments demonstrated that the snHEAzyme@DSPE-PEG2000-cRGD@Cy7 system can be effectively targeted to penetrate tumor cell membranes and treat tumors. This work offers a new perspective on snHEAzyme fabrication and its biomedical applications.