Synthesis and Functionalization of Magnetic and Gold Nanoparticles for Radiosensitization of Melanoma Cells

M. TAVERNA PORRO; C. GRISSI; I. IBAÑEZ; M. ATIA; M. F. DEL GROSSO; H. DURÁN

Buenos Aires

Workshop; NanoAndes; 2017

Malignant melanoma is the most deadly skin cancer, is highly metastatic and resistant to conventional therapies. Increased mitochondrialrespiration and reactive oxygen species (ROS) contribute to this resistant phenotype. Nanomaterialsemerge as new strategies for cancer treatment. We propose the development of combined treatments with biocompatible metallic nanoparticles (NPs) and ionizing radiation (IR) to sensitize radioresistant melanoma.Particularly, magnetic and gold NPs (MNPs and AuNPs) showgreat potential for diagnosis and therapy.The aim of this study was to synthesize, characterize and functionalize MNPs and AuNPs,to be evaluated as radiosensitizers in A375 human melanoma cells.MNPs were synthesized by the coprecipitation of Fe2+ and Fe3+ method, stabilized by methyl-PEG and characterized byTEM, X-ray diffraction, magnetometry and Mössbauer spectroscopy.Treatment of A375 cells with MNPs demonstrated no citotoxicity up to 250 µg/ml and dose-dependent increased levels of ROS. Radiosensitizing effect of 50 µg/ml MNPs was demonstrated by survival curves fitted to the linear-quadratic model (surviving fraction at 2 Gy: 0.51 for IR and 0.28 for MNPs-IR treated cells) and increased DNA damage measured by H2AX detection.Citrate-AuNPs were prepared by the Turkevich and Frens method and functionalized with thiolated PEG polymers with the mitochondriotropic residue triphenylphosphonium (TPP). AuNPs-TPP were characterized by UV?Vis spectrophotometry, DLS and TEM. AuNPs-TPP werehighly homogeneous in size and morphology and extremely stables upon storage time and exposure to high ionic strengthand showed positive Z potential values. AuNPs-TPP up to 250 µg/ml weresligthlycytotoxic in A375 cells. These results show that these novel AuNPs functionalized for mitochondrial delivery can potentially be used as radiosensitizers.In conclusion, these promising results are relevant to develop novel approaches for the control of radioresistant melanoma.