Luminescent gold nanoparticles for detection and localization in cancer cells

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Theofilou, Irene (2021). Luminescent gold nanoparticles for detection and localization in cancer cells. University of Birmingham. Ph.D.

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Abstract

Conventional imaging agents and chemotherapeutic drugs are highly associated with reduced systematic bioavailability, induced by their inefficient delivery and imprecise localization within subcellular compartments. In recent years, gold nanoparticles have attracted considerable scientific interest for potential applications in the diagnosis and treatment of cancer, due to their ability to selectively deliver imaging and therapeutic moieties to the tumor site. The multifunctionality and unique physiochemical properties of gold nanoparticles provide countless opportunities for selectively targeting tumor cells and monitoring biological processes, both at a cellular and subcellular level.
In this thesis, luminescent gold nanoparticles are presented for enhanced detection and intracellular delivery in cancer cells. Through the attachment of luminescent metal complexes to the gold surface, multifunctional nanoprobes were developed that exhibit the characteristic photophysical properties of the molecular probes. The favorable optical properties offered by the metal complex and the gold scaffold provided enhanced detection in cancer cells using multimodal imaging. Confocal luminescence imaging and transmission electron microscopy revealed the highly efficient uptake and subcellular localization of the functionalized nanoparticles in cancer cells. The ability of transition metal complexes to be easily tuned through modifying the type of ligand attached to the metal core, allowed the efficient accumulation of nanoparticles in different subcellular organelles, including mitochondria and nucleus.
The use of gold nanoparticles to improve the valency of antibodies towards antigen receptors expressed on the surface of malignant cells is also presented. The antibody coated nanoparticles were further modified with luminescent complexes to allow detection. The enhanced cellular uptake and binding affinity of the functionalized nanoparticles was evident through flow cytometry and confocal microscopy.
The detection sensitivity offered by the luminescent signal, along with the improved delivery provided by the gold scaffold, offer opportunities for monitoring biological responses upon selectively targeting cancer cells in in vivo models.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):