# Metal Nanozymes: New Horizons in Cellular Homeostasis Regulation
## 8 Metal Nanozymes in Cancer Treatment  
Cancer is one of the leading causes of death worldwide. In the last two decades, the development of nanotechnology has facilitated researchers' ability to design new nanoparticles for sensitive, rapid, and specific methods to detect and quantify cancer cells at an early stage and kill the existing tumor cells. A nanozyme can kill cancer cells in two ways. The first is direct killing by increasing ROS in vivo through the oxidase and peroxidase activities of nanozymes [192]. The second is indirect killing, which is related to the CAT or SOD activity of nanozymes by relieving the hypoxia of a tumor microenvironment (TME), aided by light, sound, or chemotherapy. It is good to remember that ROS, also called oxygen free radicals, are a side product of cellular metabolism, generated primarily by mitochondrial activity, and other sources such as xenobiotics [193], cytostatics [194], and UV-radiation [195]. In excess, ROS contribute to membrane damage by lipid peroxide formation and are part of the signaling sequence leading to apoptosis [196]. However, if not regulated properly, e.g., antioxidants, excess ROS result in oxidative stress. Consequently, this leads to damage of cellular macromolecules and inhibits cellular functions, leading to certain pathologies, including cancer [197]. The important technological advantages of nanoparticles used as drug carriers are their high stability and high carrier capacity. The ability to adjust the composition of nanoparticles to the properties of the drug makes them feasible for the incorporation of both hydrophilic and hydrophobic substances. This is of paramount importance for drug delivery because lipophilicity is a major determining factor in a compound's absorption, distribution in the body, penetration across vital membranes and biological barriers, metabolism, and excretion [198]. The surface of the NP is a target for functionalization. By modifying the NPs surface with hydrophilic moieties, one can improve NPs' stability in the biological fluids. Charged functional groups provide adequate zeta potential and prevent their aggregation and precipitation. Due to the possibility to functionalize NPs with targeting molecules, it is possible to increase the drug concentration at desired sites of action and reduce systemic levels of the drug in healthy tissues. In addition, functionalizing of fluorescent or radioactive NPs with targeting molecules allows the imaging of lesions using PET (Positron emission tomography) [199], SPECT (Single-photon emission computed tomography) [200], MRI [199, 201], and spectroscopic [202] methods. In the therapy and visualization of cancer, NPs have another very important feature: in contrast to small molecules that do not discriminate tumor and normal tissue [203], high-molecular-weight substances preferably accumulate in cancer. This is related to the specific properties of tumorous tissue: poorly aligned defective endothelial cells with wide fenestration, innervation with the wider lumen, impaired angiotensin II receptors' lack of effective lymphatic drainage [204]. At the same time, normal tissue is not permeable to big particles and quickly purified due to lymphatic clearance, the tumor tissue tends to accumulate macromolecules, especially lipids [203, 205, 206, 207]. This phenomenon has been characterized and termed the tumor-selective enhanced permeability and retention (EPR) effect. The enhancement of vascular permeability plays a critically important role in tumor growth to facilitate an adequate supply of nutrients and possibly oxygen to meet the great demands of rapidly growing tumors. Here, the vascular permeability is concerned with the macromolecular size of the drugs with which selective tumor targeting is highly enhanced. Therefore the EPR idea is now regarded as a gold standard in designing new ant-cancer agents [206].