Multifunctional nanoparticles for MR and fluorescence imaging

In the past few years a new generation of multifunctional nanoparticles (NPs) has been proposed for biomedical applications, whose structure is more complex than the structure of their predecessor monofunctional counterparts. The development of these novel NPs aims at enabling or improving the performance in imaging, diagnosis and therapeutic applications. The structure of such NPs comprises several components exhibiting various functionalities that enable the nanoparticles to perform multiple tasks simultaneously, such as active targeting of certain cells or compartmentalization, imaging and delivery of active drugs. This thesis presents two types of bimodal bio-imaging probes and describes their physical and chemical properties, namely their texture, structure, and 1H dynamics and relaxometry, in order to evaluate their potential as MRI contrast agents. The photoluminescence properties of these probes are studied, aiming at assessing their interest as optical contrast agents. These materials combine the properties of the trivalent lanthanide (Ln3+) complexes and nanoparticles, offering an excellent solution for bimodal imaging. The designed T1- type contrast agent are SiO2@APS/DTPA:Gd:Ln or SiO2@APS/PMN:Gd:Ln (Ln= Eu or Tb) systems, bearing the active magnetic center (Gd3+) and the optically-active ions (Eu3+ and Tb3+) on the surface of silica NPs. Concerning the relaxometry properties, moderate r1 increases and significant r2 increases are observed in the NPs presence, especially at high magnetic fields, due to susceptibility effects on r2. The Eu3+ ions reside in a single low-symmetry site, and the photoluminescence emission is not influenced by the simultaneous presence of Gd3+ and Eu3+. The presence of Tb3+, rather than Eu3+ ion, further increases r1 but decreases r2. The uptake of these NPs by living cells is fast and results in an intensity increase in the T1-weighted MRI images. The optical features of the NPs in cellular pellets are also studied and confirm the potential of these new nanoprobes as bimodal imaging agents. This thesis further reports on a T2 contrast agent consisting of core-shell NPs with a silica shell surrounding an iron oxide core. The thickness of this silica shell has a significant impact on the r2 and r2* relaxivities, and a tentative model is proposed to explain this finding. The cell viability and the mitochondrial dehydrogenase expression given by the microglial cells are also evaluated.

Radiative Behaviour of Gd2O3:Er/Yb nanoparticles under near infrared illumination

Upconverting nanoparticles have attracted much attention in science recently, specifically in view of medical and biological applications such as live imaging of cell temperatures or cancer treatment. The previously studied system of gadolinium oxide nanorods co-doped with erbium and ytterbium and decorated with different number densities of gold nanoparticles has been studied. So far, these particles have been proven as efficient nanothermometers in a temperature range from 300 up to 2000 K. In this work, a more detailed study on the morphological and radiative behaviour of these particles has been conducted. It was found that the laser power threshold for the onset of the black body radiation decreases strongly with the increase in the gold concentration. The temperature of the onset itself seems to remain approximately constant. The heating efficiency was determined to increase significantly with the gold concentration. The morphological study revealed that the temperature at the black body radiation threshold was not enough to induce any significant transformation in neither the nanorods nor the gold nanoparticles, as was expected from comparison with literature. However, significant changes in radiative properties and the morphology were detected for powders that underwent strong laser heating until the emission of brightly visible black body radiation.