Nanosystems for the intracellular delivery of antitumoral molecules

• Autores: Saínza Lores Touriño
• Directores de la Tesis: María de la Fuente Freire (dir. tes.)
• Lectura: En la Universidade de Santiago de Compostela ( España ) en 2022
• Idioma: inglés
• Tribunal Calificador de la Tesis: Inmaculada Conejos Sánchez (presid.), Noemi Stefania Csaba (secret.), Khairallah Alhareth (voc.)
• Programa de doctorado: Programa de Doctorado en Medicina Molecular por la Universidad de Santiago de Compostela
• Materias:
  • Química
    • Bioquímica
      • Farmacología molecular
      • Ácidos nucleicos
• Enlaces
  • Tesis en acceso abierto en: MINERVA
• Resumen

  • Cancer remains the second leading cause of death, which highlights the need to develop novel therapeutic approaches. Personalized medicine acts on specific targets of cancer cells, of which 60% are intracellular. Small molecules, which present the ability to cross biological membranes can target only the 10% of the human genome. In contrast, macromolecules, such as gene therapies and monoclonal antibodies can solve this drawback. However, an effective vector is needed to facilitate its penetration through the cellular membrane. With this in frame, the main objective of this thesis is the optimization of previously developed sphingomyelin nanosystems to associate different antitumoral agents, from small molecules to macromolecules such as plasmid DNAs, and monoclonal antibodies to achieve their intracellularly delivery into cancer cells and promote their death. Overall, this thesis proves the potential of sphingomyelin nanosystems to associate different types of antitumoral drugs, including gene therapies and antibodies, and to promote their intracellular delivery. Evidence of the enhanced therapeutic potential of this approach is provided in several preclinical models (pancreatic tumour spheroids, zebrafish embryo and mice).