Development of Multi-functional Radioprotective Nanoparticles for Salivary Glands

Objectives: Radiotherapy is widely used in clinical field to treat various types of cancer due to its non-invasiveness. However there are many serious complications caused by radiotherapy have been reported and one of them is severe salivary disfunction(Xerostomia), which negatively influence patients’ oral and even systemic health. Various drugs such as Amifostine and Tempol have been developed to protect salivary glands from irradiation but serious unpredictable complications caused by systemic injection of those drugs were reported. In this research we developed novel multi-functional nanoparticle by conjugating TAT-PEI(10kDa) and ceria oxide to mesoporous silica-coated iron oxide nanocrystals (RPMSMNP-Radioprotective mesoporous silica magnetic nanoparticle) to protect salivary glands from both short term and long term damages caused by irradiation.
Methods: Physicochemical characterization of RPMSMNPs were done by TEM, Dynamic Light Scattering, Zeta-sizer. Compelxation of pAQP5-GFP and RPMSMNPs was determined by electrophoresis gel retardation assay. Particle uptake efficiency and transfection efficiency were analyzed by FACS and confocal microscopy. Cs137 irradiation device was used to test radioprotective capability of RPMSMNPs and ROS level was measured by using DHR123 dye and spectrophotometer. Cell viability was assayed by TUNEL, Apoptosis detection kit, and CCK8. AQP5 expression level was determined by western blot and H1NMR was used to determine functional water movement through transfected AQP5-GFP.
Results: RPMSMNPs were successfully synthesized and showed approximately 50~70 nm size and +56mV zeta potential. Irradiation of Cs-source gamma ray on various salivary gland cell line (HSG, Primary cells, SMGC6) caused significant intra-cellular ROS increase, severely hampered receptor activity, decreased AQP5 expression, and increased cell death. RPMSMNPs ameliorated those phenomena by successfully scavenging intracellular ROS and upregulating functional AQP5s.
Conclusions: RPMSMNPs protected both ductal and acinar salivary gland cells from various damages caused by irradiation in vitro