Quantum Dots and Doped Nanocrystals: Synthesis, Optical Properties and Bio-applications

The aim of this thesis is to develop new luminescent nanoparticles, including quantum dots (QDs) and doped nanocrystals (NCs), for the application in biomedical research. The studies in this thesis discuss both fundamentals and the applications. Each chapter is an individual research and three parts are distinguished. The first part deals with lanthanide doped nanocrystals. Binary alkali earth sulfides CaS:Ce3+, Sm3+ and CaS:Eu2+, Sm3+ are well-known afterglow materials, and their colloidally stable nanoparticles can be afterglow nanolabels for background-free biomedical imaging. To that end, in Chapter 2, small ~10 nm CaS and SrS colloidal NCs with a narrow size distribution were made through a single source precursor method. In Chapter 3, this method was further developed for the successful synthesis of Ce3+ and Eu2+ doped CaS and SrS NCs. The use of host and dopant precursors with similar decomposition temperatures was found to be one of the key factors to successful doping. The second part studies optical properties of QDs. In Chapter 4, the temperature dependent photoluminescence properties of three highly efficient core-shell CdSe QDs were investigated at high temperatures (up to 200 °C). Thermal cycling (‘yoyo’) experiments enabled to differentiate between reversible and irreversible luminescence quenching processes. Trap state related quenching mechanism was discussed. The results in this chapter have important implications for application of QDs in optical devices working at high temperatures. The third part of this thesis contains a series of works base on QD nanoprobes which contain a QD core and dye-labeled lipids on the self-assembled lipid corona. The efficiency of the Förster resonance energy transfer (FRET) from QD core to Cy5.5 is related to the number of dye-lipids attached on the QD core. Based on this FRET platform, by monitoring the time-dependent emission profile, the dynamics of the lipids can be followed. In Chapter 5, this FRET platform was applied to study in situ the dynamics of lipid exchange and its dependence on concentration of free lipid molecules, temperature and solvent. A kinetic model was developed to describe the experimental data, and to determine the activation energy for lipid exchange on QD micelles, which is 155 kJ/mol in saline solution and 130 kJ/mol in pure water. Next, in Chapter 6, a lipoprotein-based nanoparticle with this FRET principle was developed to study in vitro the lipoprotein-lipoprotein interactions, and the lipoprotein-cell interactions. Through comparing the rate of lipid exchange between high density lipoprotein (HDL) and other lipidic nanoparticles, the stabilizing features of the apoA-I on lipid self-assembled structures is confirmed. FRET fluorescence microscopy reveals the temporal fate of lipoproteins in association with the cell. Last, in Chapter 7, this nanocrystal based FRET technology was advanced by tuning its optical features to the near infrared (NIR), for application in in vivo fluorescence imaging. This chapter reveals that lipid coated nanocrystals are dynamic structures that progressively disintegrate due to a lipid exchange process after intravenous administration. Upon vascular extravasation and accumulation in the tumour interstitium this process continues. The methods developed in this chapter can be used to evaluate differently formulated lipid coated nanocrystals and screen for compositions with improved stability, and may also contribute to enhancing the therapeutic outcome or improving the molecular imaging signature of this widely used class of nanoparticles