Cerium-Doped Self-Assembling Nanoparticles as a Novel Anti-Oxidant Delivery System Preserving Mitochondrial Function in Cortical Neurons Exposed to Ischemia-like Conditions
Valeria Nele,
Valentina Tedeschi,
Virginia Campani,
Raffaella Ciancio,
Alessia Angelillo,
Sossio Fabio Graziano,
Giuseppe De Rosa,
Agnese Secondo
Affiliations
Valeria Nele
Department of Pharmacy, University of Naples Federico II, Via D. Montesano, 80131 Naples, Italy
Valentina Tedeschi
Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatological Sciences, School of Medicine, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy
Virginia Campani
Department of Pharmacy, University of Naples Federico II, Via D. Montesano, 80131 Naples, Italy
Raffaella Ciancio
Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatological Sciences, School of Medicine, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy
Alessia Angelillo
Department of Pharmacy, University of Naples Federico II, Via D. Montesano, 80131 Naples, Italy
Sossio Fabio Graziano
Department of Pharmacy, University of Naples Federico II, Via D. Montesano, 80131 Naples, Italy
Giuseppe De Rosa
Department of Pharmacy, University of Naples Federico II, Via D. Montesano, 80131 Naples, Italy
Agnese Secondo
Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatological Sciences, School of Medicine, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy
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.
