Ceria-Manganese Oxide Nanoparticles for Protecting Salivary Gland From Radiation

Objectives: Radiation therapy is commonly used in the clinical field to treat various cancer. However, during head and neck cancer therapy, ionizing radiation can irreversibly damage salivary gland function (Xerostomia). Amifostine is widely used clinically to protect salivary gland from radiation but serious side effects such as hypocalcemia, nausea, vomiting have been reported. Furthermore, short half-life of the drugs requires repetitive treatment. When ionizing radiation is irradiated, overproduced reactive oxygen species (ROS) causes DNA oxidation, protein oxidation, lipid peroxidation and finally cell death. In this research, we synthesized ceria-manganese nanoparticles (CeMnNP) to protect salivary gland from radiation. Ceria nanoparticles play a key role in scavenging ROS through superoxide dismutase (SOD)-mimetics and catalase mimetics mechanism. Mn3O4 nanoparticles are also well known for antioxidant activity. By depositing manganese oxide nanoparticles onto cerium oxide nanoparticles surface, we could observe synergistic powerful antioxidant activity. The nanoparticles were treated prior to irradiation and protection efficacy is observed.
Methods: Physiochemical characterization of Ceria-Manganese nanoparticles (CeMnNP) was done by TEM, STEM, EDS, XPS, XRD, XAS, EELS, DLS, Zeta-Sizer. SOD mimetic activity was measured by SOD assay kit (Sigma-Aldrich) and catalase mimetic activity was measured by catalase activity assays kit (Cell Biolabs, Inc). Cs137 irradiation device was used as radiation source. Cell viability was assessed by CCK8.
Results: Synthesized CeMnNP showed around 5 nm in size. CeMnNP exhibit powerful SOD and Catalase mimetic activity. Irradiation of gamma-ray on explanted salivary gland showed significantly increased ROS levels, decreased AQP5 expression, and increased apoptosis rate leading to decrease in saliva function. Treating CeMnNP prior to radiation could effectively reduce ROS level produced from irradiation thereby minimizing apoptosis and recovering saliva function.
Conclusions: CeMnNP exhibit powerful antioxidant activity and could effectively protect salivary gland from radiation damage by scavenging overproduced ROS.