Nanorods magnètics i fluorescents de sílice mesoporosa per a usos teranòstics del fetge
- Autores: Jan Jacek Grzelak
- Directores de la Tesis: Martí Gich García (dir. tes.), Anna Roig Serra (codir. tes.)
- Lectura: En la Universitat Autònoma de Barcelona ( España ) en 2021
- Idioma: catalán
- Tribunal Calificador de la Tesis: Marianne Impéror-Clerc (presid.), Gregori Casals Mercadal (secret.), Ana Espinosa de los Monteros Royo (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
In recent years, mesoporous silica nanoparticles have been widely studied in nanomedicine as nanocarriers for diagnostic and therapeutic purposes. However, most of the research has focused on spherical particles, whereas the effect of the particle shape on the toxicity, cell uptake and biodistribution has been marginally investigated. We hypothesize that mesoporous silica-based nanomaterials with rod-like morphology could present high liver accumulation and could be used as liver-targeting agents to treat hepatic pathologies. In particular, for the early diagnosis and treatment of non-alcoholic fatty liver disease (NAFLD), which has a high and ever-increasing global prevalence.
In this dissertation, I synthesized and extensively characterized mesoporous silica rods of well-defined sizes and two distinct aspect ratios. The rods were endowed with different surface charges, functional imaging moieties and a potential therapeutic capability. I studied the toxicity, cell uptake and biodistribution of the rods using in vitro and in vivo models, assessed the imaging potential of the rods using two techniques and observed their high accumulation in the liver.
The thesis starts by discussing the state of the art on mesoporous silica particles in biomedicine, the recent works studying the influence of particle shape on the performance of silica nanocarriers, as well as current diagnosis and treatment strategies of NAFLD. Then, I focus on the synthesis of silica rods and their characterization in terms of morphology and porosity. Next, I explore strategies to load silica rods with different chemical species and report the material characterization in terms of loading efficiency, chemical and phase composition, and magnetic properties. To this aim, the rods were functionalized by synthesizing nanoparticles inside the silica pores. In particular, the synthesis of magnetic gamma-Fe2O3 nanoparticles as MRI contrast agents is discussed. Other functionalization strategies include the synthesis of ceria as a potential therapeutic agent, and trials regarding the incorporation of computed tomography and ultrasound imaging agents into the silica rods. The use of the rods as self-propelled catalytic nanomotors is also explored. Afterwards, I report the functionalization of the silica surface with amine groups endowing the rods with positive surface charge and facilitating the anchoring of fluorophores with different emission wavelengths (fluorescamine, Cyanine5) for applications in optical imaging. This is followed by the evaluation of the in vitro and in vivo toxicity, uptake and biodistribution of silica rods. The toxicity is assessed by viability studies performed on zebrafish and human liver cells, as well as by in vivo studies on zebrafish larvae and rodents. Uptake by liver cells in vitro and biodistribution in different organs in vivo is also studied. The thesis ends with general conclusions and suggestions regarding possible directions of future work.
