Development of an Au-anchored Fe Single-atom nanozyme for biocatalysis and enhanced tumor photothermal therapy

The established Au-FeSAzyme nanosystem enabled us to administer a simultaneous high-efficiency photothermal, photodynamic and chemodynamic tumour therapy in the near-infrared light. The photothermal treatment effect of the Au-FeSAzyme was pronounced. Remarkably, the glucose metabolism in the tumour site significantly blocked and down-regulated the HSP expression due to the GOD-like ability of the Au-FeSAzyme nanosystem, and the ROS production area was greatly increased, thus enhancing the photothermal, chemodynamic and photodynamic therapeutic effects. In the mouse oesophagus cancer model, the Au-FeSAzyme + laser group showed significantly lower tumour growth without apparent systemic toxicity as compared with the FeSAzyme + laser group. These results were obtained thanks to the immobilisation of Au nanozymes into the FeSAzyme through the use of this nanosystem for the first time as a new type of photothermal reagent that overcomes severe limitations of traditional photosensitisers. FeSAzyme provided new ideas for other types of photothermal therapy in the near-infrared region and to overcome the photothermal treatment defects. [Display omitted] Near-infrared light-induced photothermal therapy (PTT) can achieve effective tumor ablation, but the associated hyperthermic temperatures result in off-target inflammatory damage to proximal tissues. Therefore, killing the tumor at a lower temperature is vital to improving the clinical effect of PTT. In this study, an Au-integrated Fe single-atom nanozyme (FeSAzyme) was developed through the immobilization of an ultrasmall Au nanozyme within a metal–organic framework via an in situ reduction approach. The nanozyme was found to exhibit favorable glucose oxidase- (GOD) like activity and photosensitizing properties to better achieve low-temperature PTT. The Au-carbon nanozyme was able to markedly inhibit tumor growth both in vitro and in vivo due to its GOD-like activity and enhanced photodynamic and photothermal properties. In addition, the integration of the Au nanozyme enhanced the FeSAzyme’s peroxidase activity and catalyzed endogenous H2O2 species to generate reactive oxide species, thereby facilitating chemodynamic therapy. Furthermore, its integration markedly enhanced the PTT performance of the FeSAzyme, which achieved pronounced synergistic anti-tumor efficacy. The enzymatic activity and photothermal/photosensitive properties of the Au-FeSAzyme may help to overcome traditional therapeutic limitations, indicat