Polimers nanoestructurats basats en plati per al tractament de glioblastoma
- Autores: Xiaoman Mao
- Directores de la Tesis: Daniel Ruiz Molina (dir. tes.), Fernando Novio Vázquez (codir. tes.)
- Lectura: En la Universitat Autònoma de Barcelona ( España ) en 2021
- Idioma: español
- Tribunal Calificador de la Tesis: Patricio Gámez Enamorado (presid.), Òscar Palacios Bonilla (secret.), Alejandro Baeza García (voc.)
- Programa de doctorado: Programa de Doctorado en Ciencia de Materiales por la Universidad Autónoma de Barcelona
- Materias:
- Enlaces
- Tesis en acceso abierto en: TDX
- Resumen
Nanostructured Coordination polymers (NCPs) have emerged as a new family of nanoparticles with interesting properties due to the versatility of coordination chemistry. The multiple combinations between metal ions and organic ligands as precursors of self-assembled materials have attracted scientists for decades. The potential multifunctionality of these nanosystems and the facility for the modification of their physicochemical properties open new perspectives in different fields, including medicine. The recent advances have showed the potentiality of NCPs as smart drug delivery systems, bioimaging probes or a combination of both. The application of coordination chemistry at the nanoscale is considered one of the most versatile approaches for the development of new nanostructured materials with unprecedented properties.
This Thesis has been focused in the design, synthesis and characterization of platinum-based NCPs for exploring the possibilities of these nanosystems in the treatment of cancer, and in particular in the treatment of glioblastoma. Different platinum-based coordination polymers have been obtained and evaluated for the biomedical use based on different studies in silico, in vitro and in vivo. The synthetic methodology, the proper selection of precursors and reaction conditions, and the study of the final physicochemical and biological properties has centered the work carried out. A big effort has been put in the obtaining of chemical and colloidal stable nanoparticles in physiological conditions and in the evaluation of their therapeutic activity against glioblastoma in vitro and in vivo. For that, a multidisciplinary work has been carried out with the collaboration of specialized research groups in different areas (i.e., materials chemistry, biology, medicine). Achieving this objective was possible thanks to a proper design of the strategy followed together with a complete characterization of the prepared nanostructures and evaluation of their potentiality as anticancer nanoparticles.
In the first part of this Thesis, the nanostructuration of Pt(IV)-based coordination polymers was achieved by the coordination of a Pt(IV)-prodrug with iron(III) ions (Pt-Fe NCPs). The resulting nanoparticles were evaluated in terms of chemical and water-colloidal stability, cytotoxicity, biocompatibility and controlled drug delivery profile. Moreover, it has been evaluated their anticancer activity in vitro and in vivo, and also their potentiality for being used as MRI contrast agents. Specifically, these nanoparticles were validated by preclinical in vivo tests using GB murine models and using the intranasal administration as administration route. The nanoparticles showed interesting performance as potential anticancer agents for glioblastoma disease. On the one hand, a chemical polymerization of a catechol-based Pt(IV) prodrug was carried out to obtain a robust and colloidal stable nanoparticles. In this case, the resulting nanoparticles showed low cytotoxicity, good biocompatibility and interesting controlled drug delivery profile. These nanoparticles were evaluated for their anticancer activity against GB in vitro as alternative nanosystems to the Pt-Fe NCPs. The characteristic of this new nanosystem make it an interesting candidate to future developments.
