Glycerol-modified CeO2 ultrasmall nanoparticles conferring efficient antioxidant activity and protection against UV-induced oxidative damage

At present, the widespread biomedical application of cerium oxide nanoparticles (CeO 2 NPs) is still limited due to their tendency to aggregate in biological fluids, which reduces their specific surface area and diminishes their mimetic enzyme activities (e.g., catalase- or superoxide dismutase-like functions). In this work, ultra-small CeO 2 NPs modified by biodegradable glycerol (GCNs) were synthesized using a facile co - precipitation method at ambient temperature. The effect of glycerol modification on the physicochemical properties of ceria nanoparticles was evaluated, and it is noteworthy that the size of the GCNs decreases gradually from (8.42 ± 0.03) to (2.66 ± 0.02) nm, along with the resulting dispersibility in water improving inversely as the percentage of glycerol addition increases. In addition, the modification of glycerol also has a significant impact on the surficial electronic structure of GCNs. Compared to the unmodified CeO 2 counterparts (Ce Naked), the oxygen vacancies and Ce 3+ content of GCN–6 (66.6 wt% glycerol-modified) can be remarkably enhanced to almost twice higher than that of Ce Naked. As a result, the antioxidant activity towards scavenging 2,2-diphenyl-1-picrylhydrazyl radical (DPPH), superoxide, and hydroxyl free radicals has been significantly increased for GCN–6. In addition, HaCaT cells derived from human keratinocytes were employed to assess the cytotoxic effect and biocompatibility of GCN–6, and the HaCaT cell viability is not inhibited when the concentration of GCN–6 is less than 0.625 mg/mL. Furthermore, a reactive oxygen species (ROS) generation model was established using UVB irradiation to investigate the in vitro protective effect of GCN–6 on ROS-induced cell death. GCN–6 is proven to efficiently suppress the ROS production from oxidative stress in HaCaT cells stimulated by UVB radiation at a biocompatible concentration, indicating that the glycerol-modified GCN–6 enhances HaCaT cell survival by eliminating excessive intracellular ROS, and further providing a superior photoprotection effect against harmful UV exposure. These results suggest that surface engineering of nanoceria using biocompatible glycerol can boost a high Ce 3+ ratio, thus exhibiting potential application in protecting from oxidative stress-associated skin damage, and is promising for widespread use in sunscreens as an additive UV-shielding ingredient.