Facet-Dependent Activity of CeO₂ Nanozymes Regulate the Fate of Human Neural Progenitor Cell via Redox Homeostasis

Neural progenitor cells (NPCs) therapy, a promising therapeutic strategy for neurodegenerative diseases, has a huge challenge to ensure high survival rate and neuronal differentiation rate. Cerium oxide (CeO₂) nanoparticles exhibit multienzyme mimetic activities and have shown the capability of regulating reactive oxygen species (ROS), which is a pivotal mediator for intracellular redox homeostasis in NPCs, regulating biological processes including differentiation, proliferation, and apoptosis. In the present study, the role of facet-dependent CeO₂-mediated redox homeostasis in regulating self-renewal and differentiation of NPCs is reported for the first time. The cube-, rod-, and octahedron-shaped CeO₂ nanozymes with different facets are prepared. Among the mentioned nanozymes, the cube enclosed by the (100) facet exhibits the highest CAT-like activity, causing it to provide superior protection to NPCs from oxidative stress induced by H₂O₂; meanwhile, the octahedron enclosed by the (111) facet with the lowest CAT-like activity induces the most ROS production in ReNcell CX cells, which promotes neuronal differentiation by activated AKT/GSK-3β/β-catenin pathways. A further mechanistic study indicated that the electron density of the surface Ce atoms changed continuously with different crystal facets, which led to their different CAT-like activity and modulation of redox homeostasis in NPCs. Altogether, the different surface chemistry and atomic architecture of active sites on CeO₂ exert modulation of redox homeostasis and the fate of NPCs.