Nanomedicines for cell reprogramming in tissue engineering and immunomodulation

• Autores: Adriana Martínez Ledo
• Directores de la Tesis: Marcos García Fuentes (dir. tes.), María José Alonso Fernández (codir. tes.)
• Lectura: En la Universidade de Santiago de Compostela ( España ) en 2018
• Idioma: inglés
• Tribunal Calificador de la Tesis: Samir Mitragotri (presid.), Carmen Álvarez Lorenzo (secret.), Rosa María Hernández Martín (voc.)
• Programa de doctorado: Programa de Doctorado en Investigación y Desarrollo de Medicamentos por la Universidad de Santiago de Compostela
• Materias:
  • Ciencias médicas
    • Farmacología
      • Evaluación de medicamentos
  • Ciencias tecnológicas
    • Tecnología de materiales
      • Ensayo de materiales
• Enlaces
  • Tesis en acceso abierto en: MINERVA
• Resumen

  • The main goal of this thesis has been the development of various RNA-based therapies to modulate cell phenotypes in two different disease contexts: cancer and tissue engineering. Given the poor cell-permeability of naked RNA molecules, as well as their short half-life in biorelevant media, a critical aspect of the work has been the design and development of biomaterial-based systems intended to overcome these limitations. On the one hand, we developed a nanocarrier capable of co-allocating RNAi and chemokines to revert the tumor immunosuppression mediated by myeloid derived suppressor cells. On the other hand, we investigated a new concept of gene-activated matrices (GAMs) activated with mRNA-encoded transcription factors (TFs) to direct stem cell chondrogenic and myogenic specification. We finally optimized GAM mechanics in order to enhance TF transfection and cell differentiation driven by TF overexpression.