# Metal Nanozymes: New Horizons in Cellular Homeostasis Regulation
## 8 Metal Nanozymes in Cancer Treatment
Herein, we describe two main categories of nanozymes according to material types: metal-based nanozymes (e.g., gold, silver, palladium, platinum, and cobalt) [208] and metal oxides or metal sulfide nanozymes (e.g., cerium dioxide, ferric oxide, vanadium pentaoxide, and iron sulfide), which are applied for cancer treatment [6]. One of the best-described metals-based nanozymes are ultrasmall gold nanoparticles (AuNPs), which show oxidase, peroxidase, and catalase mimicking activities. They have been reported to show improved therapeutic effects when coupled with drug molecules [209; 210]. This is because the AuNPs have a large surface area which provides high packing capacity for drug loading and improves the hydrophilicity and stability of drugs. Furthermore, their surface can be modified by targeting ligands to enhance the tumor-selective accumulation compared to free drugs. Nanozymes can passively target neoplastic lesions with leaky neeovessels by the EPR effect. The additional advantage is the skill to control the release of loaded drugs in response to internal or external stimuli [211]. AuNPs were also reported to be effectively employed in cancer treatment by applying photodynamic therapy (PDT) and PTT [212]. For example, [PERSON] et al. constructed indocyanine green (ICG)-loaded ultrasmall gold nanoclusters (Au NCs-ICG) to modulate tumor hypoxia and augment cancer PDT and RT, respectively. In in vivo studies (4T1 tumor-bearing mouse models), the authors observed a high tumor accumulation of Au NC-ICG nanozymes visualized by near-infrared fluorescence, photoacoustic, and computed tomography imaging. They proved the potential of obtained nanozymes for the monitoring and guidance of PDT and RT. Additionally, they pointed out that the Au NCs-ICG nanozymes effectively decomposed intratumoral H\({}_{2}\)O\({}_{2}\) into O\({}_{2}\) for overcoming hypoxia [213]. Another example of metal-based nanozymes is copper hexacyanoferrate (Cu-HCF), with active single-site copper exhibits cascade enzymatic activity within TME, describe by [PERSON] et al. Their work demonstrated that Cu-HCF could amplify the killing efficacy of singlet oxygen species and suppress tumor growth in vivo [214]. Furthermore, [PERSON] et al. [215] constructed a PEGylated manganese-based SAE (Mn/PSAE) by coordinating single-atom manganese to nitrogen atoms in hollow zeolitic imidazolate frameworks. Mn/PSAE catalyzes the conversion of cellular H\({}_{2}\)O\({}_{2}\) to COH, promotes the decomposition of H\({}_{2}\)O\({}_{2}\) to O\({}_{2}\), and continuously catalyzes the conversion of O\({}_{2}\) to cytotoxic CO\({}_{2}\) via oxidase-like activity. The catalytic activity of Mn/PSAE is more pronounced in the weak acidic tumor environment; therefore, these cascade reactions enable the sufficient generation of ROS and effectively kill tumor cells. Another aspect of tumor treatment is the diagnosis of tumor tissue which is crucial in cancer detection. Metal-based nanozymes built from iron are one of the earliest inorganic nanomaterials with available catalytic behaviors [216]. Some representative examples are ferromagnetic nanoparticles which may provide critical benefits for tumor treatment, including Fenton-augmented ROS stress and hypoxia amelioration [217]. [PERSON] et al. found that magnetic ferritin nanozymes (M-HFn) can be used to target and visualize tumor tissues without any targeted ligands or contrast agents [218]. Ferritin is an iron storage protein that plays a key role in iron homeostasis and the antioxidant of cells [219]. Iron oxide nanozymes (CS-IONzyme) are encapsulated in a recombinant human heavy chain ferritin (HFn) shell, which binds to tumor cells that overexpress transferrin receptor 1 (TfR1). CS-IONzymes catalyzes the oxidation of peroxidase substrates in the presence of hydrogen peroxide to produce a chromogenic reaction for the observation of tumor tissues. They confirm that this diagnostic method detects tumor tissue with 98% sensitivity and 95% specificity.