ATP-triggered, selective superoxide radical generating oxidase-mimetic cerium oxide nanozyme exhibiting efficient antibacterial activity at physiological pH

Bacterial infections are considered as one of the major health threats to the global population. The advent of bacterial species with antibiotic resistance has attracted significant efforts to develop novel materials and strategies to effectively avoid the resistance with enhanced antibacterial potential. In this work, we have developed oxidase-mimetic cerium oxide nanoparticles (CeO2 NPs), which exhibit nanozyme activity at physiological pH in the presence of adenosine triphosphate (ATP). The oxidase-mimetic activity was confirmed to involve superoxide radicals using p-benzoquinone and dihydroethidium. Using indole propionic acid, ethanol, and terephthalic acid, it was confirmed that the oxidase-mimetic activity of CeO2 NPs with ATP does not involve the formation of hydroxyl radicals. CeO2 NPs with ATP produced a strong antibacterial activity against Staphylococcus aureus and Escherichia coli within 3 - 6 hrs. The bacterial cell morphology analysis suggested that superoxide radicals generated during the oxidase-mimetic activity of CeO2 NPs with ATP cause distortion of paired and tetrad arrangement (Staphylococcus aureus), loss of cytoplasmic content, damage, and pore formation in the cell wall (Escherichia coli) that led to the death of bacteria. Further, the live/dead assay also concludes the time-dependent death of bacterial cells with the highest death in the cell population exposed to CeO2 NPs and ATP. Thus, the antibacterial activity at physiological pH by superoxide radical generating oxidase-mimetic CeO2 NPs could be further extended to other pathogenic bacterial species.