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Tumor ablation using ionizing radiation and Pd and Au nanoparticles in Melanoma and Hepatocellular Carcinoma in vitro and in vivo

Grant number: 18/15598-2
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): July 01, 2019
Effective date (End): June 30, 2021
Field of knowledge:Health Sciences - Medicine
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Ademar Benévolo Lugão
Grantee:Lucas Freitas de Freitas
Home Institution: Instituto de Pesquisas Energéticas e Nucleares (IPEN). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Cancer is a pathological condition with high incidence, and is cause of a significant percentage of patients deaths throughout the world. Studies aiming to develop novel therapeutic approaches with more efficient and less invasive characteristics have been increasing in the last decades, and nanotechnology provides a meaningful contribution in this regard. The use of metallic nanoparticles for the enhancement of radiotherapy has been gaining attention due to the fact that the short- and long-term side effects caused by radiation therapy are considerably diminished. Radioactive nanoparticles used for anti-tumor therapy are another example of a promising therapeutic intervention on Cancer ablation, offering a more efficient control of radiation dose according to the concentration of nanoparticles administered to the patients, as well as being less invasive compared to the most common therapies, among other advantages. Furthermore, radiotherapy with a beam of charged particles leads to better outcomes than conventional photon radiotherapy, and it can be potentiated even more with if combined with the use of nanomaterials composed of metallic elements with high atomic number. This project consists of the synthesis of gold and palladium nanoparticles via reduction by epigallocatechingallate - a natural compound extracted from tea leaves - or by radiolysis, as well as their characterization and application in a superficial tumor model (Melanotic Melanoma) and deep-seated tumor model (Hepatocellular Carcinoma) in vitro and in vivo. The nanoparticles will be characterized regarding their morphology by image procedures (transmission electron microscopy, atomic force microscopy), regarding their hydrodynamic size, zeta potential and their intracellular location by confocal microscopy. B16F10 cells will be cultured in 96-well plates for the in vitro tests, and will be administered subcutaneously in the right flank of C57BL/6 micefor the induction of Melanotic Melanoma in vivo, while Hep3b cells will be cultured in 96-well plates for the in vitro tests and administered directly in the liver of athymic BALB/c nude mice for the induction of Hepatocellular Carcinoma in vivo. Several immunogenic, apoptotic, and angiogenic markers will be quantified in vitro and in vivo. A decrease in cell viability in both tumor models in vitro is expected after the administration of nanoparticles to the cell cultures, compared to the same conditions in normal fibroblasts. Furthermore, an increased survival is expected for the treated animals in consequence of the decrease of the tumor volume after the therapy with radioactive nanoparticles and with the radiotherapy potentiated by non-radioactive gold and palladium nanoparticles present in the tumor tissue. (AU)