CIOP   05384
CENTRO DE INVESTIGACIONES OPTICAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Application of Silicon Nanoparticles (SI-NPs) for Radiation- Induced Cytotoxicity via Generation of Reactive Oxygen Species (ROS)
Autor/es:
KOTLER, MÓNICA L.; GARABANO, NATALIA I.; DAVID GARA, PEDRO M.; CASAS, OSCAR R.; DODAT, DIEGO; FINKELSTEIN, S. E.; MANTZ, C.; FERNANDEZ, E.; GONZALEZ, MÓNICA C.
Lugar:
Atlanta, Georgia
Reunión:
Congreso; 55th Annual Meeting of the ASTRO; 2013
Institución organizadora:
American Society for Radiation Oncology
Resumen:
Purpose/Objective(s): Malignant glioma, the most common type of brain tumor in adults, remains resistant to current treatment strategies. The purpose of this work was to investigate the possible application of silicon nanoparticles (Si-NPs) as therapeutic tools based in its capability of increase the yield of reactive species upon irradiation (IR) of C6 glioma cells. Materials/Methods: Si-NPs uptake by C6 cells was evaluated by spectrofluorometry (SF), confocal biphotonic microscopy and transmission electron microscopy. Cell viability was measured by Neutral Red Assay. IR experiments were carried out employing a 4 MeV nominal accelerating potential Varian Clinac electron lineal accelerator. IR setup was adjusted for the cell culture to absorb 1-3 Gy. Reactive oxygen species (ROS) production was assessed by an oxidation-sensitive probe, CM-H2DCF-DA. Results: Internalization of Si-NPs measured by SF was observed after a lag period of 2 h incubation, reaching a threefold increase after 6 h. Under these conditions, Si-NPs were localized mainly in liposomes. Cytotoxic analysis of Si-NPs performed at different concentrations (0-50 mg/mL) during 2-12 revealed a 50% decrease in cell viability for 50 mg/ mL, 12 h (p < 0.001) suggesting Si-NPs cytotoxicity was significantly lower than numerous other nanoparticles used in biological studies. Then, Si-NPs treated cells (25, 50 mg/mL and 6 h incubation) underwent IR at variable doses (0-2 Gy) and cell viability was measured. C6 cells exposed to 50 mg/mL of Si-NPs for 6 h showed a 36% decrease in cell viability; a further 15% diminution was observed when irradiated with 1 Gy dose, lower than the standard dose delivered to the cancer patients (2 Gy)(p < 0.01). Finally, ROS generation evaluated in C6 cells exposed to 50 mg/mL of Si-NPs for 6 h and irradiated at 1-3 Gy indicated that ROS generation increases with IR dose, reaching a 700% at 3 Gy. Conclusions: These data suggest Si-NPs can be applied for to advance IR cytotoxicity via generation of ROS. With optimization, Si-NPs have the potential to be used as radiosensitizers to improve the outcomes of existing cancer radiation therapy by employing lower IR doses with a consequent decrease in damage to healthy tissue. Future work will address specific targeting of Si-NPs to tumoral tissues to further potentiate these beneficial properties.