In this thesis, new approaches directed towards simple and functional imaging agents (IAs) for magnetic resonance (MR) and fluorescence multimodal imaging are proposed. In Chapter 3, hybrid silver nanostructures (hAgNSs), grown using a polyamino carboxylic acid scaffold, namely 1,4,7,10-tetraaza-1-(1- aminobutyl)-4,7,10-triacetic acid cyclododecane (AB-DO3A), are described. The engineered hAgNSs consist of a “large” silver nanoparticle (AgNP, stabilized by the AB-DO3A scaffold), which can act both as a template for surface modification and potentially as a therapeutic agent, and “smaller” Ag nanoclusters (AgNCs) that can be used as optical trackers due to their fluorescent properties. The use of (similar) aggregated organic ligands as nucleation points for the formation of protein cages of the cowpea chlorotic mottle virus (CCMV) is described in Chapter 4. Stable assemblies are engineered by pure hierarchical self-assembly of micelles of the 1,4,7,10-tetraza-1-(1- carboxymethylundecane)-4,7,10-triacetic acid cyclododecane (DOTAC10) ligand inside CCMV. These purely self-assembled protein cages show enhanced ionic and capsid r1 relaxivities which are attributed to aggregation and altered micelle association kinetics resulting from local confinement inside the protein cage. In Chapter 5, the synthesis, characterization and study of the cytotoxicity of multimodal gold nanorods (MMAuNRs) for MR and optical imaging is described. The gold nanostructures were characterized using UV-Vis absorption spectroscopy, TEM and total reflection X-ray fluorescence (TXRF). The MMAuNRs obtained are biocompatible, show median lethal concentration (LC50) values > 150 pM AuNR, improved relaxivity properties, high Gd3+ loadings and can be optically colocalized with mouse myoblast (C2C12) cells in vitro. In Chapter 6, functionalized carbon-based organic scaffolds are proposed as platforms for multiple lanthanide complexation, taking advantage of the chemically similar, but electronically/magnetically different, properties lanthanides show. Initially, a water-soluble anthracene core bismacrocyclic ligand is used to show its potential as a proof-of-principle probe. Moreover, the covalent attachment of the AB-DO3A template (Chapter 3) to carbon nanotubes (CNTs) was studied. The preliminary characterization and evaluation of the properties of these functionalized carbon-based scaffolds show promising results, thereby highlighting their potential for multimodal imaging purposes. Finally, the future perspectives and challenges ahead for these metal complex-based templates, nanostructures and the multimodal IAs described in this thesis are briefly discussed.
|Qualification||Doctor of Philosophy|
|Award date||2 Nov 2012|
|Place of Publication||Enschede|
|Publication status||Published - 2 Nov 2012|