# Metal Nanozymes: New Horizons in Cellular Homeostasis Regulation
## 9 Nanozymes Combating Pathogens
Next, CS-IONzyme strongly stimulates nasal epithelial cells (ECs) to secrete chemokine CCL20 via TLR 2/4 pathway, which recruits more DCs into the submucosal regions to form TEDs for H1N1 WIV uptake. After viral capture, DCs gradually reach the phenotypic and functional maturation and then quickly migrate into draining cervical lymph nodes (CLNs) for antigen presentation. Finally, the antigen-specific immune response is initiated. Reprinted from [268] with the permission of [PERSON] under the Creative Commons license (CC BY 4.0). Currently, the antiviral effect of many metallic nanoparticles is known [269; 270]. The knowledge on this subject has expanded recently due to numerous studies conducted in connection with the COVID-19 pandemic [271; 272; 273]. For example, the mitochondrial proteins of the virus can be degraded by the multivalent silver nanozymes [274]. Silver ions bind to the RNA virus genome to activate antiviral mitochondrial proteins [270]. Gold nanozymes have the ability to mimic the virus-binding receptor, leading to virus deformation [275]. Zinc oxide nanozymes are also able to reduce viral infection by enhancing T cell and antibody responses [276; 277]. Overall, nanozymes seem to be an effective alternative for detecting and targeting viruses, including coronaviruses; however, the catalytic mechanisms are poorly understood and require research in nanotechnology, computational engineering, machine learning, artificial intelligence, and computer science. Nanozymes also offer hope to overcome diseases caused by parasites, although this field of science is only emerging. Among the few reports on this subject, of special interest is the work [PERSON] and [PERSON] [278], who constructed a ferritin nanozyme (Fenozyme) composed of recombinant human ferritin (HFn) protein shells that specifically target blood-brain barrier endothelial cells (BBB ECs) and the inner Fe\({}_{3}\)O\({}_{4}\) nanozyme core that exhibits ROS-scavenging CAT-like activity. When administered to mice with experimental cerebral malaria, Fenozyme significantly increased the survival rate, protecting BBB ECs from ROS damage and reducing parasitemia by polarizing macrophages to the M1 phenotype. The Fenozyme colocalized with CD31, an adhesion molecule normally found on BBB endothelial cells. Moreover, Fenozyme binding to endothelial cells was largely blocked by an anti-HFn receptor antibody. The accumulation of Fenozyme in the brains of mice occurred in a time-dependent manner. Fluorescence imaging showed that Fenozyme could specifically bind to macro- and micro-vasculature in the brain. In summary, the HFn envelope bound the HFn receptor and directed the fenozyme to BBB endothelial cells in the mouse brain. Fenozyme localized inside the endosomes, presumably through HFn receptor-mediated endocytosis to function as a catalase in the endothelial cells. While 50 uM of H\({}_{2}\)O\({}_{2}\) killed approximately 50% of the model endothelial cells, the addition of Fenozyme almost fully protected the cells from the damage induced by H\({}_{2}\)O\({}_{2}\) at the concentration of 0.1 mg/mL. In addition, co-administration of Fenozyme and antimalarial arterienther alleviated encephalopathy and memory impairment in mice that survived the experimental cerebral malaria [278]. These results demonstrated the importance of ROS-induced stress in parasite-caused inflammation and indicated that the nanozymes could be used as an adjuvant in parasitic diseases.