# Metal Nanozymes: New Horizons in Cellular Homeostasis Regulation
## 2 A Short History of Nanozymes  
The term \"artificial enzyme\" was used by [PERSON] in 1970 for a chemical structure combining a metal catalytic group and a hydrophobic binding cavity of a polysaccharide [12], while the term \"nanozyme\" was first used in 2004 by [PERSON] et al. for triazacyclonane-functionalized gold nanoparticles that have been used as catalysts for phosphate ester transphosphorylation [13]. The essence of the catalytic action of this enzyme boils down to the interaction of Zn\({}^{2+}\) ions on the surface of gold nanoparticles and inspired researchers in this developing field. Another example of using catalytic systems with an activity similar to the enzyme is described in 2007 by [PERSON] et al. [14], where the intrinsic enzyme peroxidase-like activity of magnetic nanoparticles (Fe\({}_{3}\)O\({}_{4}\)) was utilized in an immunoassay. This discovery used the same element atoms with different valences on the nanoparticle surface for catalytic reactions. In addition, numerous studies have revealed that various metal and metal oxide nanoparticles (such as iron, cerium, and gold oxide nanoparticles), carbon nanomaterials (including carbon nanotubes and graphene oxide), and many organometallic structures exhibit excellent catalytic properties by mimicking structures or functions of natural enzymes [4; 15; 16]. Together, these nanozyme systems offer higher catalytic stability, ease of modification, and lower production costs in a variety of biomedical applications compared to natural enzymes (see, e.g., [4; 15; 17; 18]). Nanozymes can be divided into three categories according to material types: metal-based nanozymes (e.g., gold, platinum, and cobalt), metal oxides or metal sulfide nanozymes (e.g., ferric oxide, cerium dioxide, vanadiumpentoxide, and iron sulfide), and carbon-based  
Figure 1: The emerging roles of nanozymes in cellular biology. nanozymes, (e.g., fullerenes, graphene, and carbon dots). Herein, according to the keynote of the special edition, we focus on the metal- and metal-oxide-based nanozymes. The catalytic reaction of nanozymes is like that of natural enzymes, which conforms to the kinetic curve of Michaelis-Menten equation. Kinetics analysis performed by researchers [19; 20; 21; 22; 23] indicated that nanozymes showed typical Michaelis\(-\)Menten behavior toward H\({}_{2}\)O\({}_{2}\), TMB (3,3,5,5-tetramethylbenzidine) glucose and other substrates. The selected examples of the K\({}_{\text{m}}\) (Michaelis-Menten constant) values and V\({}_{\text{max}}\) (maximum rate) of the reaction for certain substrates are shown in Table 1 (see also [19]). The redox properties of metal and metaloxide nanozymes are mainly responsible for their regulatory action, analogous to natural enzymes containing metal centers. Recently, however, the possibility of regulating their auxiliary properties, such as lipophilicity, stereospecificity, and the ability to respond to destination-specific stimuli, has gained increasing importance. Similar to natural enzymes, the activities of nanozymes can be tuned by many factors, such as pH [25; 26], temperature [26], surrounding environment [27], and the type of the metal ion [26]. One class of such easily tunable substances are organometallic frameworks (MOFs). They are a class of coordination polymers containing metal ions/clusters linked by coordination bonds with organic ligands organized into a repeating structure and have aroused great interest in researchers over the past decades. It must be mentioned that the particular interest in MOFs is not only due to their catalytic activity but also to their regulated structures and morphologies, excellent surface areas, high porosity and crystallinity, high loading capacity, thermal/chemical stability, and tunable affinity, which makes them functionally even more similar to natural enzymes. Studies of activities mimicking the enzymes of catalytic nanoparticles based on metals and their oxides gained popularity in the last decade and are currently in the phase of expon