Enzyme-like CeO₂ Nanomaterials with DifferentStructure–Activity for Ulcerative Colitis Therapy

Cerium dioxide nanomaterials (CeO₂ NMs) have been widely reported as nanozymes to improve homeostasis of the gut microbiota in ulcerative colitis mice. However, the structure–activity relationship of CeO₂ NMs in terms of their physiochemical properties and biological activities remains unclear. This study showed that the gas–liquid interface played an important role in the synthesis of CeO₂ NMs by controlling crystal growth, leading to extension of the crystal nuclei in different directions. We therefore synthesized three CeO₂ NMs with different properties in nitrogen (CeO₂–N₂), carbon dioxide (CeO₂–CO₂), and oxygen (CeO₂–O₂) conditions, respectively, and studied their structure–activity relationships. The results showed that all CeO₂ NMs helped to prevent and control microbial damage, including changes in microbial growth and metabolite contents, to varying extents. The repair capacities of CeO₂ NMs with different properties were mainly attributed to their nanozyme catalytic abilities. The codelivery of CeO₂ NMs loaded with 5-aminosalicylic acid (5-ASA), especially CeO₂–N₂ NMs, could improve the metabolite products and homeostasis of the gut microbiota. These results showed that codelivery of CeO₂ NMs loaded with 5-ASA could help to alleviate gut inflammation in ulcerative colitis mice. We anticipate that CeO₂ NMs may provide a therapeutic option in future clinical trials.