Biological and spectroscopic studies of fluorescent
Doctoral thesis, UCL (University College London).
Semiconductor nanoparticles, often referred to as quantum dots (QDs), have attracted considerable interest due to their unique photophysical properties such as high photostability and fluorescence quantum yields. In the biomedical arena, QDs are being studied both for their diagnostic and therapeutic applications, in particular the possibility of using QDs in photodynamic therapy, which is based on the destruction of tissue with light through photosensitised formation of reactive oxygen species (ROS). In this thesis, the ability QDs to induce the formation of ROS through Type I photoinduced electron transfer and Type II energy transfer mechanisms was investigated. Firstly, the effectiveness of quantum dot-photosensitiser complexes for photosensitised production of ROS was investigated. A sulfonated phthalocyanine was found to form stable complexes with water soluble pegylated quantum dots. Efficient Förster resonance energy transfer (FRET) between the quantum dot and phthalocyanine was demonstrated to generate singlet oxygen by the Type II mechanism with a quantum yield of up to 0.15. Secondly, the potential of QDs alone to produce ROS in aqueous solutions and cellular environments was studied. In aqueous solution, the production of superoxide radical anions by photoinduced electron transfer to molecular oxygen was demonstrated with a quantum yield of 0.005. The yield could be significantly enhanced via a Type I mechanism in the presence of the electron transfer agent, NADH, which was demonstrated by oxygen consumption measurements, electron paramagnetic resonance (EPR) spin trapping and cytochrome c reduction. Production of hydroxyl radicals was shown using a fluorescence probe. In the cellular studies, QD uptake could be significantly enhanced by conjugation with the cell penetrating Tat peptide, which enabled studies of phototoxic effects induced by QD photosensitised ROS production. QDs can also be used as fluorescent imaging probes in vivo for a variety of biological applications; however their fluorescence properties in tissue have not been widely investigated. The uptake of intravenously administered CdSeTe/ZnS QDs in a range of organs including liver, was investigated. By comparing a range of fluorescence quantitation methods, including fluorescence microscopy and chemical extraction, it was found that these QDs were highly resistant to degradation under physiological conditions, demonstrating their effectiveness as imaging probes in vivo.
|Title:||Biological and spectroscopic studies of fluorescent nanoparticles|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Surgery and Interventional Science (Division of) > Research Department of General Surgery|
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