New biomaterials for the design of nanomedicines that modulate glioblastoma stem cells

Abstract

Gene therapy emerged in the 70s as an alternative to small drugs and proteins in the treatment of a large variety of diseases, but the administration of nucleic acids still remains a challenge due to the biological barriers that need to be overcome before reaching the target cells. Indeed, polynucleotides are very sensitive to degradation and cannot cross cell membranes. To overcome these obstacles, nucleic acids are often included in viral, lipid or polymeric particles. The objective of the thesis has been the development of new prototypes of polymeric nanoparticles for their use in gene therapy and to test their potential for the treatment of glioblastoma. For this, a variety of commercially available and synthetic cationic polymers have been combined with plasmid DNA and an endosomolytic polymer, nanoparticles were characterized for their physicochemical properties, for their toxicity and transfection efficiency in cell cultures. The prototype with better results regarding their transfection/toxicity ratio was used with a therapeutic plasmid encoding Bone Morphogenic Protein 4 as a potential treatment in vitro and in vivo against glioblastoma.