Gold nanoparticles coated by mixtures of ligands: a basic study and their functionalization with gadolinium complexes

In the last twenty years, gold nanoparticles (AuNPs) have received a tremendous attention for applications in the biomedical field for diagnosis, therapy, imaging and drug delivery. Among the numerous studies on AuNPs a huge interest was focused on understanding and controlling the properties of these hybrid organic-inorganic nanoparticles. This studies are pushed by the fact that AuNPs can be easily synthesized with a good control over the size, shape, dispersity and composition. Moreover, AuNPs can be protected by different ligands which influence their properties and their interaction with the environment. Indeed, considering that in most cases AuNPs present on the surface mixtures of ligands, it is very important to know not only the relative amount of ligands present into the monolayer, but also how mixtures of ligands can organize on the surface of the gold core. This thesis is focused on two projects. The first one deals with the study of the morphology of mixed monolayers composed of hydrogenated and fluorinated ligands of different lengths and bulkiness. Previously, our group have demonstrated through ESR experiments that mixtures of immiscible ligands phase segregate forming domains. It was found that the shape of these domains depends on the dimension of the gold core, on the relative length and ratio between the ligands and on the ligand composition. The objective of this PhD research project is to study in depth the organization of mixed monolayers protected gold nanoparticles, in particular using blends of hydrogenated and fluorinated thiols. To this aim, we have designed and synthesized AuNPs protected by three classes of binary mixtures of ligands: blend of thiols having different length (NPs-C12/F6 and NPs-C16/F6); ligands having the same length (NPs-C12/F10 and NPs-C8/F6) and nanoparticles protected by ligands of different length and similar bulkiness (NPs-brC12/F6). We have obtained mixed monolayers with different compositions, varying the initial ratio between the two ligands. For all this nanoparticles we have recorded different 19F-NMR experiments. The chemical shift variation with the nature of ligands and the monolayer composition reveal to be very diagnostic. The obtained results were supported by in silico experiments, in collaboration with the group of dott. P. Posocco, prof. S. Pricl and prof. M. Fermeglia of the University of Trieste, in order to predict the shape of the domains of each type of nanoparticles. The second project is focused on AuNPs for MRI applications. Nuclear magnetic resonance is a powerful technique for investigating physiopathology in vitro and in vivo. It is a non-invasive technique and permit to obtain images using non-radioactive tracers. There are two main classes of materials which have been developed for this technique: compounds to promote the relaxivity of water protons like gadolinium chelates or iron oxide particles (SPIOs) used for 1H-MRI and fluorinated compounds (PFCs) used for 19F-MRI. Previously in our group have been reported AuNPs protected by water soluble fluorinated ligands for 19F-MRI applications. This nanoparticles present suitable features for MRI and are also able to bind hydrophobic molecules allowing their applications for imaging and drug delivery. We have decided to improve the characteristics of these nanoparticles in order to have smaller T1 relaxation time and consequently better performances in the magnetic resonance field. In this thesis, we will present in Chapter 4 new preliminary results about three classes of AuNPs for MRI applications: AuNPs protected by fluorinated ligands, AuNPs protected by ligands which complex the Gd (III) and AuNPs protected by fluorinated ligands able to bind Gd(III). Additionally, we have designed and synthesized new thiols used for the synthesis of AuNPs suited for 1H-MRI and 19F-MRI.