Platinum Engineering on Nanoceria Surface toward High Catalytic Activity for Inducing Tumor Cell Apoptosis and Inhibiting Migration

Abstract

Nanozymes have shown great clinical application potential in the treatment of tumors with reactive oxygen species (ROS). However, conventional nanozyme technologies face challenges such as low catalytic activity and unknown therapeutic mechanisms for tumor therapy. Herein, we designed platinum (Pt)/nanoceria (CeO 2 ) hybrid nanozymes using Pt single-atom and cluster engineering on the CeO 2 surface, named Pt/CeO 2 -NR and Pt/CeO 2 -R respectively. The results showed that Pt/CeO 2 -R had higher enzyme-like activity than Pt/CeO 2 -NR because the Pt clusters (Pt 0 and Pt 2+ ) stabilized the oxygen vacancies better than the single Pt atoms (Pt 2+ ). Further studies showed that Pt/CeO 2 -R exhibited selective toxicity to tumor cells, induced tumor cell apoptosis, and inhibited cell migration. In addition, we studied the antitumor mechanism of Pt/CeO 2 -R with stable isotopic labeling by amino acids in cell culture (SILAC)-based quantitative proteomics. Mechanistically, large amounts of the ROS produced by Pt/ CeO 2 -R affected both the mitochondria and the endoplasmic reticulum and ultimately induced tumor cell apoptosis. Additionally, Pt/CeO 2 -R inhibited tumor cell migration by downregulating the proteins on the cell membrane surface. This study provided an approach for optimizing the enzyme-like activities of CeO 2 through the efficient use of platinum engineering, and explored the mechanisms by which Pt/CeO 2 -R killed tumor cells and inhibited cell migration during the treatment of tumors.