Accelerating Ce3+/Ce4+ Conversion in CeO2 via Mn doping to Endow Scaffolds with Chemodynamic Therapy Properties

Abstract

CeO2 nanozymes have garnered significant attention in chemodynamic therapy due to their peroxidase-like activity and ability to deplete glutathione. However, their catalytic efficiency is constrained by the low conversion rate of Ce3+/Ce4+. To overcome this limitation, the electron transfer was accelerated by introducing the transition metal Mn atom as a valence electron donor through lattice charge transfer. In detail, we introduced Ce1-xMnxO2 into the poly-L-lactic acid (PLLA) scaffold fabricated by selective laser sintering. The conversion from Ce3+ to Ce4+ promoted the decomposition of H2O2 within the tumor microenvironment to generate hydroxyl radicals with high oxidative activity, consequently inducing oxidative stress. The conversion from Ce4+ to Ce3+ depleted intracellular antioxidant glutathione, disrupting redox balance in tumor cells. This continuous redox cycle ultimately triggered apoptosis in tumor cells. Using a first-principles Hubbard-corrected approximate density-functional method, the analysis of the electron band structure revealed the presence of donor energy levels within the bandgap of Ce1-xMnxO2, enabling electron transfer channels around 0.645 eV. Electrochemical experiments confirmed that Ce0.8Mn0.2O2 significantly reduced the activation overpotential from 0.907 V to 0.646 V, enhancing its redox capacity. As a result, the scaffold exhibited a threefold increase in tumor-killing rate. These findings highlight the immense potential of CeO2 nanozymes in enhancing chemodynamic therapy for effective tumor treatment.