One of the biggest challenges for the biomedical applications of cerium oxide nanoparticles (CeNPs) is to maintain their colloidal stability and catalytic activity as enzyme mimetics after nanoparticles enter the human cellular environment. This work examines the influences of CeNP surface properties on their colloidal stability and catalytic activity in cell culture media (CCM). Near-spherical CeNPs stabilized via different hydrophilic polymers were prepared through a wet-chemical precipitation method. CeNPs were stabilized via either electrostatic forces, steric forces, or a combination of both, generated by surface functionalization. CeNPs with electrostatic stabilization adsorb more proteins compared to CeNPs with only steric stabilization. The protein coverage further improves CeNPs colloidal stability in CCM. CeNPs with steric polymer stabilizations exhibited better resistance against agglomeration caused by the high ionic strength in CCM. These results suggest a strong correlation between CeNPs intrinsic surface properties and the extrinsic influences of the environment. The most stabilized sample in CCM is poly(acrylic acid) coated CeNPs (PAA-CeNPs), with a combination of both electrostatic and steric forces on the surface. It shows a hydrodynamic diameter of 15 nm while preserving 90% of its antioxidant activity in CCM. PAA-CeNPs are non-toxic to the osteoblastic cell line SAOS-2 and exhibit promising potential as a therapeutic alternative.
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