Mn–Ce Synergy Promoting Defective Hollow CeO 2 Nanospheres Amplifies the ROS Storm for Tumor Therapy

The regulation of the valence states and surface vacancy defect concentrations is crucial for enhancing the catalytic activity of cerium-based nanozymes. Herein, Mn-doped cerium dioxide hollow nanospheres with a mesoporous surface (denoted as M-CeMn0.5) were synthesized using a tannic acid chelation and sacrificial template method. The mesoporous surface structure of the M-CeMn0.5 nanozymes provides abundant active sites for catalytic reactions. Results indicate that the synergistic effect between Mn and Ce promotes the generation of increased Ce3+ species and oxygen vacancies on the CeO2 surface. Furthermore, Mn doping enhances the electron transfer rate during catalysis, which ensures excellent peroxidase (POD)-like activity of M-CeMn0.5 in both chemical and cellular environments. Moreover, in vitro experiments demonstrated that M-CeMn0.5 catalyzes the decomposition of H2O2 in the tumor microenvironment (TME) into •OH and •O2– via a Fenton-like reaction. This process resulted in a killing efficiency of 65.6% against MCF-7 cells while also exhibiting good biosafety. This study provides a strategy for developing efficient and safe nanozymes and improves the efficacy of metal oxide nanozymes in combination cancer therapy.