The pH-dependent multiple nanozyme activities of copper-cerium dioxide and its application in regulating intracellular oxygen and hydrogen peroxide levels

Cu doped CeO2 (Cu-CeO2) nanoparticles were synthesized via the hydrothermal method, exhibiting multiple nanozyme activities such as good oxidase-like (OXD), peroxidase-like (POD) and catalase-like (CAT) activities. These Cu-CeO2 nanoparticles were successfully utilized to modulate the levels of oxygen and hydrogen peroxide in cells. The OXD and POD mimics showed optimal at pH of 3.5 and 4.0, but their activities significantly decreased under neutral or slightly acidic conditions. On the other hand, the CAT activity was excellent at pH 6.5, while the OXD and POD mimics were less effective. These findings demonstrated that nanozyme activity of Cu-CeO2 nanoparticles is pH-dependent. Consequently, within the microenvironment of tumor cells, the CAT can efficiently catalyze the conversion of H2O2 into O2, unaffected by H2O2/O2 consuming mimics. Both oxygen indicator and oxygen tester measurements confirmed a significant increase in O2 levels in phosphate-buffered saline (PBS). Furthermore, confocal microscopic imagings using fluorescence probes for H2O2 and O2 validated the variations of H2O2/O2 in cells. This study highlights the ability of Cu-CeO2 to regulate intracellular reactive oxygen levels and its tremendous potential in nanotherapy and alleviating tumor hypoxia.