The Influence Of The Material And The Geometry Of Nanoparticles On Their Organ Distribution And Biological Barrier Passage

Abstract

The interest of nanomaterials for biomedical applications is even more increasing. Several strategies utilising nanoparticles (NPs) to deliver drugs have been widely characterised in these last two decades. In spite of the potential offered by NP-based therapy (e.g. prolonged biodistribution, active target therapy, reduced toxicity, combined diagnosis and therapy), many hurdles hampered the passage from the bench to the bedside. To build up safe and reliable devices, a hierarchical characterisation of the interactions with what NPs will encounter on their way toward the therapeutic target (biological fluids, cells, and organs) is fundamental, even before the loading of the drug. Unfortunately, this aspect is often neglected and the lack of standardised characterisation methods limits the possibility of clearly elucidating the potential of nanomaterials to be used as drug carriers. The aim of my thesis was to investigate how NP physicochemical features such as the material, size, shape and surface functionalization can influence their biodistribution and their passage through biological barriers upon systemic administration in healthy mice. The results of my thesis confirmed a size- and shape- dependent effect of hard NPs to the overall biodistribution. Small spherical gold NPs showed a progressive accumulation over time at variance with larger NPs that accumulated from the beginning in vital organs. On the contrary, Ultrasmall silica NPs preferentially underwent a kidney filtration. They escaped from resident macrophages and therefore did not accumulate in the liver and spleen. Moreover, our findings gave rise doubts about the contribution of the geometry and the functionalization on the passage across the blood-brain barrier after intravenous administration of NPs.