Enhancing Antioxidants Performance of Ceria Nanoparticles in Biological Environment via Surface Engineering with o-Quinone Functionalities
Pierluigi Lasala, Tiziana Latronico, Umberto Mattia, Rosa Maria Matteucci, Antonella Milella, Matteo Grattieri, Grazia Maria Liuzzi, Giuseppe Petrosillo, Annamaria Panniello, Nicoletta Depalo, Maria Lucia Curri, Elisabetta Fanizza
Abstract
The development of ceria (CeO2−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 CeO2−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 (CeO2−x@Cit) and post-treatment with dopamine hydrochloride (CeO2−x@Dopa). The concept behind this work is to enhance via surface engineering the intrinsic antioxidant properties of CeO2−x NPs. For this purpose, thanks to electron transfer reactions between dopamine and CeO2−x, the CeO2−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 CeO2−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. CeO2−x@Dopa demonstrated less efficiency in DPPH· scavenging (%radical scavenging activity 13% versus 42% for CeO2−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 CeO2−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 CeO2−x NP surface to DPPH·, within cells the presence of o-quinone groups contributed with CeO2−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 CeO2−x NPs, enhancing their effectiveness in biological systems by promoting additional redox pathways.