Cerium-Doped Self-Assembling Nanoparticles as a Novel Anti-Oxidant Delivery System Preserving Mitochondrial Function in Cortical Neurons Exposed to Ischemia-like Conditions

Neurodegenerative diseases are characterized by mitochondrial dysfunction leading to abnormal levels of reactive oxygen species (ROS), making the use of ROS-scavenging nanomaterials a promising therapeutic approach. Here, we combined the unique ROS-scavenging properties of cerium-based nanomaterials with the lipid self-assembling nanoparticles (SANP) technology. We optimized the preparation of cerium-doped SANP (Ce-SANP) and characterized the formulations in terms of both physiochemical and biological properties. Ce-SANP exhibited good colloidal properties and were able to mimic the activity of two ROS-scavenging enzymes, namely peroxidase and super oxide dismutase. Under ischemia-like conditions, Ce-SANP could rescue neuronal cells from mitochondrial suffering by reducing ROS production and preventing ATP level reduction. Furthermore, Ce-SANP prevented mitochondrial Ca2+ homeostasis dysfunction, partially restoring mitochondrial Ca2+ handling. Taken together, these results highlight the potential of the anti-oxidant Ce-SANP platform technology to manage ROS levels and mitochondrial function for the treatment of neurodegenerative diseases.

Automated summary

Neurodegenerative diseases are characterized by mitochondrial dysfunction and abnormal levels of reactive oxygen species (ROS). In this study, we developed cerium-based nanomaterials with ROS-scavenging properties and combined them with lipid self-assembling nanoparticles (SANP). These cerium-doped SANP (Ce-SANP) showed good colloidal properties and mimicked the activity of ROS-scavenging enzymes. Ce-SANP rescued neuronal cells from mitochondrial damage under ischemic conditions by reducing ROS production and preventing ATP level reduction. Furthermore, Ce-SANP restored mitochondrial Ca2+ handling and showed potential for the treatment of neurodegenerative diseases by managing ROS levels and mitochondrial function.