DESIGN, SYNTHESIS AND CHARACTERIZATION OF FUNCTIONALIZED METAL NANOPARTICLES FOR APPLICATIONS IN MELANOMA TREATMENT

TAVERNA PORRO, MARISA; IBAÑEZ, IRENE L.; ATIA, MARIEL; GRISSI, CECILIA; DURÁN, HEBE

Mar del Plata

Congreso; Reunión Conjunta de la Sociedad Argentina de Investigación Clínica (SAIC), la Sociedad Argentina de Inmunología (SAI) y la Sociedad Argentina de Fisiología (SAFIS) 2018; 2018

SAIC, SAI, SAFIS, Sociedad Argentina de Virología (SAV), NANOMED-ar, International Society of Neuroimmunomodulation, Society of Mucosal Immunology

Malignant melanoma is the most deadly skin cancer, is highly metastatic and resistant to conventional therapies.Advances in nanomaterials contributed in recent years to the development of new strategies for cancer treatment.In this context, we have envisioned the use of two types of metallic nanoparticles: Magnetic nanoparticles (MNPs) and gold nanoparticles (AuNPs), both designed for the treatment of refractory melanoma. MNPs are highly biocompatible, stable and can be directed under an external magnetic field. Moreover, incubation of cells with MNPs can increase intracellular levels of reactive oxygen species (ROS). We demonstrated that the combined treatment of MNPs and ionizing radiation (IR) induces cytotoxic oxidative stress and sensitizes melanoma cells. On the other hand, targeting cancer metabolismhas emerged as a promising therapeutic strategy. In this context, multi-resistant melanoma cells have increased mitochondrial respiration and high level of ROS. Disruption of this metabolism, in combination with IR, could be an effective means for this highly resistant cancer. However, mitochondrial targeting of therapeutic agents is still challenging. A way to overcome this limitation is by using nanoparticles. AuNPs are also highly biocompatible, passively accumulate in tumors by enhanced permeability and retention effect and can also be modified for selective mitochondrial active targeting. In addition, they possess unique electronic properties that make them excellent radiosensitizing agents. We demonstrated that AuNPs functionalized with the mitochondriotropic residue triphenylphosphonium, in combination with IR, radiosensitize radioresistant melanoma cells. In conclusion, our results show that these novels metallic functionalized NPs can potentially be used as radiosensitizers for refractory melanoma treatment. Due to their interesting physicochemical and biological properties, these types of NPs could be promising for the development of multifunctional platforms for cancer diagnosis and therapy.