# Metal Nanozymes: New Horizons in Cellular Homeostasis Regulation
## 4 Strategies in the Quest for New Nanozymes  
Almost all of the metals and their oxides in block d (and many of block f) of the periodic table are useful as redox catalysts mimicking natural enzymes. The important quality in the research seems to consist not so much in proving the catalytic abilities of subsequent metallic nanoparticles and metaloxides but in the use of a set of structural solutions in experimental design (Figure 4). This brings particularly interesting effects that inspire new approaches to nanozyme catalysis, allowing very selective activities of nanozymes, as was the case in an interesting work of [PERSON] et al. [76] on discrete hafnium metal-oxo cluster [Hf18O10(OH)26(SO4)13*(H2O)33] (Hf18), centered by the hexamer motif found in many MOFs. This water-insoluble nanoparticle acts as a heterogeneous catalyst for the efficient hydrolysis of horse heart myoglobin (HHM), inducing a strictly selective cleavage at directed protein sites. Among 154 amino acids present in the sequence of HHM, cleavage at only six solvent-accessible aspartate residues was observed. The hydrolytic activity was likely derived from the actuation of HfUV Lewis acidic sites and the Bronsted acidic surface of Hf18, by a heterogeneous reaction. The selective hydrolysis of proteins by nonenzymatic catalysis is difficult to achieve, yet it is crucial for applications in biotechnology and proteomics. An important aspect of searching for new catalytic nanoparticles is careful observation and inspiration with naturally occurring processes. For example, one of the reasons why  
Figure 4: Approaches in the design of new nanozymes. natural enzymes contain mostly d-block metals is the valence flexibility of the latter. Therefore, bioinspired nanomaterials that show great potential for constructing novel nanozyme catalysts are those based on molybdenum. The main valence states of Mo include Mo (0), Mo (III), Mo (IV), Mo (V), and Mo (VI). No wonder then that this extremely valence-flexible metal is an essential trace element and nutrient in bacteria, plants, and animals serving as a cofactor for various Mo-based enzymes such as xanthine dehydrogenase, aldehyde oxidase, sulfite oxidase (SuOx), and nitrate reductase (NRase) [77]. The classes of bioinspired Mo-based nanozymes so far include molybdenum disulfide (MoS\({}_{2}\)) [78; 79] molybdenum selenide (MoSe\({}_{2}\)) [80] molybdenum oxide (MoO\({}_{x}\), \(2\leq x\leq 3\)) [81], molybdenum carbide (Mo\({}_{2}\)C) [82; 83], and hybrid Mo-based nanomaterials (TiO\({}_{2}\)@MoS\({}_{2}\)/CoFe\({}_{2}\)O\({}_{4}\), Au-Pd/MoS\({}_{2}\), MoS\({}_{2}\)/GO, MoS\({}_{2}\):CeO\({}_{2}\), etc.) [84; 85; 86; 87]. The MoO\({}_{x}\) NPs were first reported to have oxidase (OXD)-like catalytic activity, and the MoS\({}_{2}\) NSs were reported to have peroxidase-like activity [78; 88]. MoSe\({}_{2}\) and hybrid Mo-based nanozymes were then found to possess various enzyme-like activities, including POD, OXD, CAT, SOD, and RNase [80; 81; 89; 90]. [PERSON], [PERSON], et al. [91] successfully used cysteine-protected nanodots MoS\({}_{2}\) with CAT and SOD catalytic properties for protection against ionizing radiation. The electrochemical measurements of cysteine-protected MoS\({}_{2}\) dots evidenced their strong in vitro catalytic activities in H\({}_{2}\)O\({}_{2}\) and oxygen reduction reactions. Viabilities of mouse fibroblast cells treated with MoS\({}_{2}\) dots in different doses under exposure to gamma rays were significantly increased. The in vivo experiments showed that the surviving fractions of mice can be significantly increased with exposure to gamma rays (7.5 Gy; 76% survival at the dose of 50 mg/kg vs. 0% for non-treated irradiated mice). The oxidation state of the metal is a decisive factor influencing the nanozyme activity, as shown in the research of [PERSON] et al. [92]. The authors obtained the porous LaNiO\({}_{3}\) nanocubes. The 3+ oxidation state of Ni was shown to be superior to Ni\({}^{0}\) and Ni\({}^{2+}\) for the nanozymes' catalytic activities.