In the recent past, the remarkable capabilities of cerium oxide nanocrystals (CeO2 NCs) have been harnessed in the realm of nanotherapeutics, particularly because of their unique electronic structure that induces the generation of oxygen vacancies (Vo). These Vo acting as reactive sites at the surface of CeO2 NCs, furnish them as oxygen reservoirs and prime candidates for oxidative stress mitigation.[1] Engineering the intrinsic structure of CeO2 NCs, have steered possibilities of inhibiting ROS build-up and toxicity issues. Thus, in this research, a comprehensive investigation is carried out to unveil the significance of structure-functionality interplay to enhance the antioxidant efficacy and minimalize the dose-dependent side effects of CeO2 NCs. 

The novel Vo – rich CeO2 NCs were synthesized by a rapid wet-chemical process in a batch reactor assembly with varying surface Ce3+ concentration by appropriately tailoring the particle size at acidic pH, under a kinetically controlled-non-equilibrium environment. This facilitated in significantly enhancing the colloidal stability, which was discerned from the size dependent-zeta potential (-34.1±5.3 mV to -26.1±7.8 mV) and were in accordance with the Derjaguin-Landau-Verwey-Overbeek model. The monodispersity and the crystallinity of the as-prepared ovular CeO2 NCs was evident from the TEM images, revealing an average particle size of 4.5 nm. The calculated lattice fringe spacing for (200) was 0.27 nm. The 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•) scavenging assay was utilized to ascertain the potency of CeO2 NCs for mitigating oxidative stress. The half-maximal inhibitory concentrations (IC50) of NCs of varying sizes are illustrated in Figure 1. Further, the DPPH• scavenging efficacy (IC50 ranging from ~ 1.43 to ~ 3.72 μg/mL) exhibited by the NCs (of varying doses and Ce3+ concentrations) is evinced from the UV-Visible absorption spectra and agrees well with the speedy colour transition from violet to yellowish-orange. The spectral changes are akin to the interfacial proton-coupled-electron-transfer (PCET) mechanism.[2] PCET implies the accelerated affinity of reduced CeO2 NCs to transfer an electron along with H+ from the solution, which is most prominent at the highest Ce3+ concentration and dose. These insights elucidated the remarkable radical scavenging activity that makes these Vo – rich CeO2 NCs a coveted and cost-effective nanotherapeutic agent for alleviating oxidative stress-mediated ailments.