Enhancing Antioxidants Performance of Ceria Nanoparticles in Biological Environment via Surface Engineering with...

The development of ceria (CeO_2-x)-based nanoantioxidants requires fine-tuning of structural and surface properties for enhancing antioxidant behavior in biological environments. In this contest, here ultrasmall water-dispersible CeO_2-x nanoparticles (NPs), characterized by a high Ce³⁺/Ce⁴⁺ ratio, were synthesized in a non-polar solvent and phase-transfer to an aqueous environment through ligand-exchange reactions using citric acid (CeO_2-x@Cit) and post-treatment with dopamine hydrochloride (CeO_2-x@Dopa). The concept behind this work is to enhance via surface engineering the intrinsic antioxidant properties of CeO_2-x NPs. For this purpose, thanks to electron transfer reactions between dopamine and CeO_2-x, the CeO_2-x@Dopa was obtained, characterized by increased surface Ce³⁺ sites and surface functionalized with polydopamine bearing o-quinone structures as demonstrated by complementary spectroscopic (UV-vis, FT-IR, and XPS) characterizations. To test the antioxidant properties of CeO_2-x NPs, the scavenging activity before and after dopamine treatment against artificial radical 1,1-diphenyl-2-picrylhydrazyl (DPPH^·) and the ability to reduce the reactive oxygen species in Diencephalic Immortalized Type Neural Cell line 1 were evaluated. CeO_2-x@Dopa demonstrated less efficiency in DPPH^· scavenging (%radical scavenging activity 13% versus 42% for CeO_2-x@Cit before dopamine treatment at 33 μM DPPH^· and 0.13 mg/mL loading of NPs), while it markedly reduced intracellular ROS levels (ROS production 35% compared to 66% of CeO_2-x@Cit before dopamine treatment with respect to control-p < 0.001 and p < 0.01, respectively). While steric hindrance from the dopamine-derived polymer layer limited direct electron transfer from CeO_2-x NP surface to DPPH^·, within cells the presence of o-quinone groups contributed with CeO_2-x NPs to break the autoxidation chain of organic substrates, enhancing the antioxidant activity. The functionalization of NPs with o-quinone structures represents a valuable approach to increase the inherent antioxidant properties of CeO_2-x NPs, enhancing their effectiveness in biological systems by promoting additional redox pathways.