King, Siobhan Marie (2020). Iridium nanoparticles for multichannel luminescence lifetime imaging, mapping localization in live cancer cells. University of Birmingham. Ph.D.
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King2020PhD.pdf
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Abstract
The development of long-lived luminescent nanoparticles for multiphoton lifetime imaging is of high interest in cancer research especially for in vivo experiments which allows for quantification of angiogenesis and cancer metastasis. Multiphoton imaging can reach up to several millimetres in depth detection, thus providing invaluable information on tumour vasculature and the microenvironment of the tumour. Detection of luminescence lifetimes is extremely sensitive to local environmental changes and is independent of probe concentration. Luminescent cyclometalated iridium(III) complexes were conjugated onto gold nanoparticles to produce novel multiphoton lifetime imaging nanoprobes. These nanoprobes show characteristic long luminescent lifetimes from the iridium(III) complex in the range of hundreds of nanoseconds and a short-lived signal on the scale of picoseconds from the gold, allowing for multichannel detection of these nanoprobes through lifetime imaging. This is the first report of multichannel phosphorescence and fluorescence lifetime imaging being applied to functionalised gold nanoparticle within cancer cells. The sensitivity of the iridium signal on the local environment of the cell was used to successfully map localisation within HeLa cells. The combination of the sensitivity of the iridium signal to the cellular environment together with the targeting nanoscaffold to guide delivery, offer opportunities for iridium nanoparticles to be used for targeting and tracking in in vivo models. The ability for these nanoprobes to selectively target cancer cells was investigated by conjugating monoclonal antibodies and SiRNA. Multiphoton lifetime imaging revealed uptake of these nanoprobes into cancer cells, and detection of luminescence lifetimes were sensitive to local changes in the environment. These functionalised nanoprobes were investigated in applications for selectively targeting angiogenesis in cancer.
| Type of Work: | Thesis (Doctorates > Ph.D.) | |||||||||
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| Award Type: | Doctorates > Ph.D. | |||||||||
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| Licence: | All rights reserved | |||||||||
| College/Faculty: | Colleges (2008 onwards) > College of Engineering & Physical Sciences | |||||||||
| School or Department: | School of Chemistry | |||||||||
| Funders: | Engineering and Physical Sciences Research Council | |||||||||
| Subjects: | Q Science > QD Chemistry | |||||||||
| URI: | http://etheses.bham.ac.uk/id/eprint/10373 |
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