Contribución a las tecnologías hipertérmicas mediadas por nanopartículas para terapias anticancerígenas

Abstract

of the thesis of Oscar Ernesto Simon Casanova Carvajal, presented as partial requirement to obtain the DOCTOR degree in BIOMEDICAL ENGINEERING.Madrid, June 28 th, 2017. CONTRIBUTION TO HYPOTHERMAL TECHNIQUES MEDIATED BY NANOPARTICLES FOR ANTICANCERIC THERAPIESAbstract:After the fusion of nanotechnology with medicine and bioengineering, fields of research in nanomedicine and nanobioengineering were created, which broadened the perspective of medical research and emerging new frontiers. These investigations have allowed new methods of approach to find solutions to long-standing human biological problems and the development and administration of therapeutic or pharmacological diagnoses. To achieve this, nanoparticles have been developed, which are miniaturized agents, which have given way to nanomedicine. The gold nanoparticles used in this study are nanorods (GNR) coated with G protein, a common receptor for mechanically anchoring antibodies. In this research hyperthermia plays a role of greatest importance which refers to the application of heat to destroy malignant cells by induction of apoptosis through the denaturation of proteins and the rupture of cell membranes. The application of gold nanoparticles generated by optical hyperthermia improve in-vitro therapy, and considerable advances were made in-vivo for animal models. In magnetic hyperthermia, the conversion of electromagnetic energy into heat generated by SPIONs subjected to alternating magnetic fields (HAC) can be used to cause the death of tumour cells. Recent studies have shown that the magnetic response, and therefore the heating efficiency of SPIONs, are significantly reduced when these nanoparticles are placed in viscous carrier liquids and within living cells or biological tissues. The higher viscosity of the biological environment and the spatial distribution or agglomeration of nanoparticles within the intracellular organelles strongly influence the efficacy of SPIONs to increase the temperature of the surrounding medium. These factors that arise from the nanobio-interaction make the heating efficiency in in-vivo applications less efficient and predictable than in ideal ferrofluids. Considerable advances were made in both techniques, in optical hyperthermia it was included until obtaining improvements in the introduction of dispersant material and biocompatible light such as Silica. The results suggested a considerable improvement in all the variables involved in the system such as irradiated power, time of exposure to the laser, concentration of gold nanoparticles (nanorods) and maintaining the mortality rate in cancer cells (CT2A) against cell lines considered healthy (MC3T3). In the case of magnetic hyperthermia, an electronic system was designed and built to generate excitatory waveforms different from conventional ones (sinusoidal), tolerance tests were carried out on the nanoparticles that will be used in the system. Also, it was demonstrated the existing physical phenomenon when the SPIONs are phagocytized by the cells, applying an intrace...