RADIOSENSITIZATION OF HUMAN MELANOMA CELLS BY SUPERPARAMAGNETIC IRON OXIDE NANOPARTICLES

CECILIA GRISSI; MARISA TAVERNA PORRO; MARINA PERONA; SERGIO MORENO; JOAQUIN SACANELL; MARIELA DEL GROSSO; IRENE IBAÑEZ; HEBE DURÁN

Congreso; Reunión Anual de Sociedades de Biociencias 2022: Sociedad Argentina de Investigación Clínica (SAIC), la Sociedad Argentina de Inmunología (SAI) y la Sociedad Argentina de Fisiología (SAFIS); 2022

Melanoma is the deadliest form of skin cancer, highly metastatic and resistant to therapies. Superparamagnetic iron oxide nanoparticles (SPIONs) have shown great potential for diagnosis and therapy. The aim of this study was to evaluate the radiosensitizing effect of SPIONs in A375 human melanoma cells. SPIONs were synthesized and stabilized by methyl-poly(ethylene glycol). After that, it was physicochemically characterized by transmission electron microscopy, X-ray diffraction, magnetometry and tested in vitro. Superparamagnetic behavior and low dispersion in shape and sizes (8-17 nm) were obtained. No cytotoxicity was found in A375 cells exposed up to 250 µg/ml for 24 h. Dichloro-dihydro-fluorescein diacetate assay revealed higher reactive oxygen species levels in treated cells (p<0.05). Survival curves obtained by combined treatments of SPIONs and gamma irradiation (137Cs) (SPIONs-IR) and fitted to the linear-quadratic model, demonstrated a significant increase in radiation effect in SPIONs-IR treated cells (p<0.05), with surviving fraction at 2 Gy of 0.51 and 0.28 for IR and SPIONs-IR treated cells, respectively. Increased DNA damage by SPIONs-IR vs IR was observed by the detection of γH2AX foci at 30 minutes post-irradiation and a decreased repair capacity was found at 24 h post-irradiation by analyzing the persistence and size increase of γH2AX foci in SPIONs-IR compared with IR treated cells (p<0.05). In conclusion, SPIONs proved to be effective radiosensitizers of melanoma cells.