Direct Synthesis of Cerium Oxide Nanoparticles in Reducing Sugars: Enhanced Ce3+ Surface Density for Biological Application

Cerium oxide nanoparticles (CNPs) are recognized for their ability to scavenge reactive oxygen species (ROS), making them promising candidates for mitigating oxidative damage in biomedical applications. However, many conventional synthesis methods limit the formation of Ce³⁺ states, which are critical for this antioxidant function. Building upon previous findings that glucose can promote Ce³⁺ formation, this study investigates the broader impact of both reducing (glucose, fructose, galactose) and non-reducing (dextran, sucrose, cyclodextrin) natural sugars on CNP synthesis. CNPs were synthesized in the presence of these sugars, and the surface densities of Ce³⁺ were measured. Results showed that reducing sugars significantly increased Ce³⁺ surface density compared to controls, enhancing the redox-active nature of the nanoparticles. Superoxide dismutase (SOD) assays further demonstrated a correlation between higher Ce³⁺ ratios and increased biological activity, affirming the functional importance of redox modulation. Biological evaluation in human bone marrow-derived mesenchymal stem cells (hMSCs) revealed no cytotoxic effects from any CNP formulation. Notably, sugar-modified CNPs at low concentrations enhanced alkaline phosphatase (ALP) activity and calcium deposition, as confirmed by ALP and Alizarin Red S (ARS) assays, key indicators of osteogenic differentiation. Overall, the study underscores the therapeutic potential of Ce³⁺-rich, sugar-modified CNPs for promoting bone growth and broadens their applicability in regenerative medicine.