The impact of gadolinium doping on physicochemical properties and neuroprotective activity of polyacrylic acid conjugated cerium oxide nanoparticles - in vitro study of potential theranostics for neurodegenerative diseases.

BACKGROUND

Cerium oxide nanoparticles (CeO NPs) are showing neuroprotective effects in various experimental models of neurodegeneration. Doping of nanoparticles with magnetic resonance imaging (MRI) contrast agents (e.g., gadolinium) could enable simultaneous diagnosis and treatment of neurodegenerative diseases, a technology called theranostics that is used primarily in oncology but can also be successfully applied in the diagnosis and treatment of neurodegenerative diseases.

METHODS

In this study, we doped polyacrylic acid conjugated cerium oxide nanoparticles with gadolinium (Gd-CeO) to create a theranostic agent with MRI capabilities and neuroprotective properties. These nanoparticles were evaluated for their physicochemical characteristics, magnetic resonance imaging potential, biosafety profile, cellular uptake, and neuroprotective effects compared to CeO nanoparticles (CeO) in a human neuronal model of Parkinson's disease employing undifferentiated and retinoic acid-differentiated SH-SY5Y cells.

RESULTS

The synthesized Gd-CeO nanoparticles showed good stability, concentration-dependent T1 and T2 contrast features, and were not cytotoxic. The Gd-CeO nanoparticles were rapidly taken by cells and maintained neuroprotective potency against hydrogen peroxide (H2O2)- and 6-hydroxydopamine (6-OHDA)-induced cell damage to a similar extent as did CeO nanoparticles without Gd doping. Moreover, we demonstrated a protective effect of Gd-CeO and CeO nanoparticles on mitochondrial membrane potential, DNA fragmentation, and the number of necrotic cells in both models of cell injury, whereas at the level of caspase-3 activity, we showed an inhibitory effect of the studied NPs only in the 6-OHDA model. Finally, the protection mediated by Gd-CeO and CeO nanoparticles against H2O2 was confirmed in mouse primary cortical neurons.

CONCLUSIONS

Since the developed Gd-CeO nanoparticles showed promising contrast features, as well as maintaining biosafety and neuroprotective properties similar to those of nanoparticles without Gd doping, they could be further investigated as a potential theranostic probe for neurodegenerative diseases, including Parkinson's disease.