Enzyme-like CeO₂ Nanomaterials with Different Structure–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.