Tunable phosphate-mediated stability of Ce3+ ions in cerium oxide nanoparticles for enhanced switching efficiency of their anti/pro-oxidant activities

Abstract

Switching of the Ce³⁺/Ce⁴⁺ oxidation states in cerium oxide nanoparticles (CNPs) provides various superior nanozyme activities. However, nanozymes lack a switch to reversibly regulate the multi-nanozyme capacity depending on physiological/pathological environments, e.g. different pH and H₂O₂ levels. Furthermore, highly concentrated Ce³⁺ ions with abundant oxygen vacancies (V_o) in CNPs have the potential to enhance their catalytic activities, but the phosphate anions (P) adsorbed on Ce³⁺ ions block their several catalytic activities. This study, therefore, demonstrates that the tunable P-mediated stability of Ce³⁺ ions involves the superoxide dismutase (SOD) mimetic activity of CNPs, and leads to enhanced switching efficiency of their anti/pro-oxidant activities. Herein, highly concentrated Ce³⁺ ions in V_o-CNP layers (V_o-CNPLs) were fabricated, and the threshold conditions necessary to alter the stability of Ce³⁺ ions treated with P were explored by X-ray photoelectron spectroscopy. P-adsorbed Ce³⁺ ions (P-Ce³⁺) in V_o-CNPLs were efficiently destabilized in H₂O₂ solution (pH 5–6) rather than in HCl and HNO₃ solutions (pH 3), and the presence of H₂O₂ readily released P from Ce³⁺ sites. Indeed, though P-Ce³⁺ temporarily arrested the SOD mimetic activity to generate H₂O₂ (linked to anti-oxidant activity) at physiological pH, they did enable the initiation of SOD mimetic activity (pro-oxidant activity) even at pH 5 close to biologically-appropriate acid conditions, e.g. in lysosome/endosome/tumor-microenvironments. These findings suggest that P-Ce³⁺ ions enhance the switching efficiency of their anti/pro-oxidant activities. Thus, P-mediated switches could be utilized to achieve a better understanding of the nanozyme switching-mechanisms, and for the design of multi-functional nanozymes for enhancing therapeutic efficacy.