# Metal Nanozymes: New Horizons in Cellular Homeostasis Regulation
## 3 Mechanisms of Pro-Oxidative and Antioxidant Action of Nanozymes
There are attempts to achieve this by combining, quenching, or coating nanoparticles with classic chain-breaking antioxidants, such as tocoperhoids (vitamin E) [51], flavonoids [52; 53], ascorbate (vitamin C [54; 55]), aromatic amines [56], and nitroxides [57]. Some other nanomaterials could by themselves scavene radicals on their surface or exert antioxidant properties (e.g., Au, Ag, CeO\({}_{2}\), and Pl NPs). The antioxidant activity of metal-based nanoparticles can be related to those of natural enzymes. There are several types of antioxidant enzymes in the cellular system, such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPX), peroxiredoxin, etc. [58]. These antioxidant enzymes play an important role in maintaining cellular redox balance. Many nanomaterials have catalytic effects similar to those of antioxidant enzymes. This interesting antioxidant property of some nanomaterials is intended to be used in nanomedical applications ([PERSON] et al., 2010, [PERSON] et al., 2012). As reviewed by [PERSON] et al. [26], among the various antioxidant nanoparticles reported to date, metal oxide nanozymes have proven to be effective candidates in mimicking the antioxidant activities of first-line enzymes, i.e., SOD, CAT, and GPX. Based on the reaction mechanism, nanozymes can be divided into two main families: 4 (i) the oxidoreductasetase family and (ii) the hydrolase family. The oxidoreductasetase mimetic nanozymes catalyze the oxidation reaction in which reducing agents and oxidants act as electron donors and acceptors, respectively. Among the metallic nanoparticles that exhibit oxidoreductase activity are nanoparticles of platinum [59], cerium oxide [60], iron oxide [61], and others. Hydrolase nanozymes catalyze the hydrolysis reaction by cleaving chemical bonds. In this process, the larger molecule dissociates into two smaller molecules. For example, gold nanoparticles are widely used as common nanoenzymes of hydrolases to catalyze the hydrolysis reaction [62; 63; 64]. Nanozymes can also be classified into (i) antioxidants and (ii) pro-oxidants [65]. In biological systems, the pro-oxidant induces oxidative stress by producing free radicals. For example, the presence of a transition metal can generate a hydroxyl radical (HO\({}^{\bullet}\)) by Fenton chemistry [66]. Antioxidant nanozymes clean or scavene free radicals using CAT-like or SOD-like actions. Superoxide (OO\({}^{\bullet}\)) decays at a low pH as the result of the reaction between its protonated and deprotonated form (Equation (1), k = 8.9 \(\times\) 10\({}^{7}\) M\({}^{-1}\) s\({}^{-1}\) in H\({}_{2}\)O), while at low pH and in organic solvents, decisive is the reaction between two molecules of the protonated form (Equation (2), k = 7.6 \(\times\) 10\({}^{5}\) M\({}^{-1}\) s\({}^{-1}\) in H\({}_{2}\)O). \[\mathrm{O_{2}}^{\bullet-}+\mathrm{HOO}^{\bullet}+\mathrm{H^{+}}\rightarrow \mathrm{O_{2}}+\mathrm{H_{2}O_{2}}, \tag{1}\]  
\[\mathrm{HOO}^{\bullet}+\mathrm{HOO}^{\bullet}\rightarrow\mathrm{O_{2}}+ \mathrm{H_{2}O_{2}}, \tag{2}\]  
The self-decomposition of peroxide is thus highly pH-dependent, with a maximum rate at pH = 4.5, and becomes slower with increasing pH. At physiological pH = 7.4, this reaction has an apparent rate constant of 2 \(\times\) 10\({}^{5}\) M\({}^{-1}\) s\({}^{-1}\). Meanwhile, even a small amount of HOO\({}^{\bullet}\) can initiate lipid peroxidation and cause radical damage to biomolecules. Thus, the SOD activity is important, catalyzing the decomposition of the dangerous reactive peroxide radical. The SOD mimetic catalyzes the dismutation of superoxide anions to hydrogen peroxide, which in turn can be converted to molecular oxygen and water by a catalase-like nanozyme. On the other hand, peroxidase mimetic can convert hydrogen peroxide into hydroxyl free radicals. Peroxidase-like activity is demonstrated, among others, by iron oxide nanocomposites [67; 68; 69; 70] and iron-containing nanomaterials [71]. These materials are widely used for glucose detection [72; 73].