Towards the therapeutic use of nanoparticles in cancer: a cellular perspective

• Autores: Antonio Aranda Ramos
• Directores de la Tesis: C. Nogués i (dir. tes.)
• Lectura: En la Universitat Autònoma de Barcelona ( España ) en 2021
• Idioma: inglés
• Tribunal Calificador de la Tesis: María Elena Ibáñez de Sans (presid.), Andreu Blanquer Jerez (secret.), Tania Patiño Padial (voc.)
• Programa de doctorado: Programa de Doctorado en Biología Celular por la Universidad Autónoma de Barcelona
• Materias:
  • Ciencias de la vida
    • Biología celular
  • Ciencias tecnológicas
    • Tecnología de materiales
      • Ensayo de materiales
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• Resumen

  • For the past three decades, nanotechnology has been an ever-growing field, including its application to medicine, what is known as nanomedicine. Despite the promising potential applications of nanomedicine, translation to effective therapeutic and diagnostic alternatives is still very low. This is in part, due to a lack of knowledge of the mechanisms in which nanomaterials interact with the organisms, beginning with their biointeraction at the cellular level. This information is often over-looked when characterising new engineered nanomaterials and can contribute to their efficient and safe development. In this scenario, the goal of this thesis is to provide an in-depth clear perspective from a cellular point of view of these nanomaterial bio-interactions and how they might affect their expected therapeutic outcome. We also point out the importance of using compatible methods to study the cytotoxicity of new nanomaterials to avoid potential assay interferences and to evaluate the uptake and intracellular fate of nanomaterials quantitatively. Works presented in this thesis highlight the importance of in vitro characterisation of the biointeraction of nanomaterials using different cell lines. First, we proved the biocompatibility and antioxidant properties of cerium oxide nanoparticles, achieving antioxidant results close to those obtained with commercially available antioxidant products. Second, we demonstrated the biocompatibility of silica nanoparticles and provided new insights into their biointeraction using confocal laser scanning and scanning electron microscopy techniques and a novel quantifiable analysis of the obtained internalisation data. It also led new quantitative information on how time-dependent internalisation can critically affect the uptake and intracellular fate of nanomaterials. Lastly, we analysed the biointeraction, cytotoxicity, magnetic targeting capabilities and hyperthermia-triggered therapeutic use of iron and gold magnetoplasmonic polystyrene nanodomes to selectively treat tumoral cell lines (SKBR-3) and leave non-tumoral cell lines (MCF10a) unaffected. The efficiency to magnetically manipulate this kind of nanoparticles and the increase of the uptake efficiency in cells is proved in static and flow conditions. We also highlight the differential cell death mechanisms induced by hyperthermia after near-infrared laser irradiation between tumoral and non-tumoral cell lines. In conclusion, the present thesis provides new knowledge towards the development of better nanomaterials and new generation diagnostic and therapeutic agents for the selective destruction of malignant cells.