Silsesquioxanes and Silica Nanoparticles as Platforms for Fluorine and Gadolinium Based Contrast Agents for Magnetic Resonance Imaging

Abstract

Magnetic resonance imaging (MRI) is an important diagnostic tool for the imaging of soft tissues. The non-invasive technique of MRI allows for the detection of tumors, infections and injuries at an early stage. New opportunities for medical diagnosis and magnetic resonance (MR) imaging techniques are offered with the use of hybrid nanomaterials. The functionalization of a nano-sized material, e.g. with paramagnetic Gd(III) chelate complexes for 1H imaging or with 19F containing molecules for 19F imaging leads to a high concentration of contrast agents, which can be obtained at low volumes. In the first part of the work T8-silsesquioxanes were functionalized with polyorganofluorinated groups (PFG). By different synthetic pathways highly symmetrical polyorganofluorinated POSS cubes (PF-POSS) which generate a sharp singlet in the 19F spectrum were obtained. The properties of the PF-POSS cubes in dependency of their PFG structures, the resulting solubility and their hydrolysis stability were investigated. Additionally, in vitro measurements as well as post mortem experiments were performed for chosen examples. In the second part of this work the size dependent properties of spherical and monodisperse silica nanoparticles (SNPs) with diameters of about 15, 50 and 130 nm were examined for their application as potential contrast agents (CAs) for magnetic resonance imaging (MRI). Therefore the SNPs were covalently functionalized with two different lanthanoid(III) (Ln = Gd) DOTA chelate complexes via an aminopropyl linker. Measurements, inter alia dynamic light scattering (DLS), zeta potential and scanning electron microscopy (SEM) were carried out to investigate surface interparticle interactions and the influence of surface charges. In order to evaluate an optimal particle size, the expected increase in relaxivity due to the Gd(III) surface payload was examined. The surface loading with Gd(III) chelates was varied for the smaller SNPs by repeating the coupling procedure. Furthermore the modification of the surface charge of all SNPs was performed by acetylation of remaining surface functional groups. The longitudinal and transverse relaxation rates (r1 and r2) of the SNPs were investigated by MRI at 3 Tesla in agar phantoms.