# Metal Nanozymes: New Horizons in Cellular Homeostasis Regulation
## 9 Nanozymes Combating Pathogens  
Bacterial infections continue to be a growing global health problem affecting millions of people every year [237; 238], and the most commonly used treatment regimens are limited to antibiotics, which increases multidrug resistance. The antimicrobial activity of nanozymes also offers potential for the development of new antimicrobial agents. Many reports on such an action can be found in the latest literature, and examples of application trials are discussed below. The antimicrobial mechanism of nanozymes depends mainly on the activity of peroxidase and oxidase catalyzing the decomposition of H\({}_{2}\)O\({}_{2}\) to \({}^{\bullet}\)OH in order to regulate ROS [239; 240; 241; 242]. Through redox activity, nanozymes generate highly toxic ROS, including free radicals, hydrogen peroxide, superoxide anion, and singlet oxygen, which can destroy the integrity of cell membranes or damage bacterial DNA (Figure 10). Nanozymes also catalyze the degradation of a wide variety of molecules, including polysaccharides, lipids, proteins, and extracellular DNA in the bacterial biofilm matrix. Again, the changes of the nanoenzyme architecture, metal oxidation states, and physicochemical parameters determine the enzyme action in a decisive manner. For example, [PERSON] and [PERSON] [243] designed two kinds of copper/carbon nanozymes, with copper states tuned from Cu\({}^{0}\) to Cu\({}^{2+}\). Cu or CuO was deposited on hollow carbon spheres. The authors demonstrated that the nanozymes exhibited peroxidase-, catalase-, or superoxide dismutase-like activities dependent on the copper state. Interestingly, results indicated that the different enzymatic activity modes resulted in different antibacterial modes of action against bacteria. For the CuO nanozymes, the released Cu\({}^{2+}\) ions caused membrane damage, lipid peroxidation, and DNA degradation of Gram-negative bacteria, whereas the Cu\({}^{0}\)-based NP induced the generation of ROS via peroxidase-like catalytic reactions, determining their effect against both Gram-positive and Gram-negative bacteria [243]. In terms of nanoparticle architecture, promising effects gave nanozyme defect modulation, analogous to defect engineering, applied in electronics industrial catalysis and photocatalysis [245]. In the cited study, [PERSON], [PERSON] et al. Developed a procedure for obtaining defect-rich adhesive nanozymes which, due to their special surface properties, tend to trap bacteria and have effective antibacterial properties (Figure 11). The defect-rich, adhesive nanozyme was constructed by using MoS\({}_{2}\) nanozymes as nanobuilding blocks and copper nanowires (Cu NWs) as a support, while resulting in a rough surface for bacteria trapping and more active defect-rich edge sites which improved peroxidase-mimicking activity. These nanozymes showed increased antibacterial activity against both drug-resistant Gram-negative _E. coli_ and Gram-positive _Staphylococcus aureus_. Moreover, their use in vitro and in vivo has been demonstrated, with a strong antibacterial effect and good biocompatibility. Possessed strong near-infrared (NIR) absorbance and outstanding photothermal effects with a rapid elevating temperature under 808 nm light irradiation, which improved their therapeutic potential. Due to their excellent bacterial binding capacity and efficient catalytic activity, defect-rich adhesive nanozymes pave the way for the development of alternative antibiotics. Similarly, [PERSON], [PERSON] et al. reported that Cu\({}_{2}\)MoS\({}_{4}\) nanoplates showed NIR-II light enhanced catalytic activity similar to oxidase and peroxidase, which caused an 8 log reduction in _E. coli_ titer and a 6 log reduction in _S. aureus_ titer after only 10 min in an in vitro system. Moreover, Cu\({}_{2}\)MoS\({}_{4}\) showed excellent therapeutic efficacy against _S. aureus_ infection in vivo with negligible toxicity to red blood cells and mice.