Developing methods to image non-flourescent anticancer cylinders in cancer cell lines

[摘要] In this thesis, biological and imaging studies have been carried out on a supramolecular helicate (iron cylinder) and indirect methods to image this non-fluorescent compound have been developed. The iron cylinder has been investigated as a quencher of nuclear Hoechst fluorescence in a range of cancer cell lines. Flow cytometry and epifluorescence data has shown quenching occurring in a concentration-dependent manner at both the population and cellular level. These results provide evidence for the cylinder being able to interact in close proximity to the DNA within 20 minutes of administration. Using luciferase-expressing breast cancer cells, the iron cylinder has been shown to directly affect light emission in a concentration-dependent manner, an inhibition that has not previously been investigated providing further opportunities for imaging by monitoring the inhibition of luminescent enzymes. Furthermore, iron cylinder has been shown to quench GFP fluorescence using fluorimetry and confocal microscopy providing novel possibilities supporting the imaging of non-fluorescent compounds indirectly through the use of fluorescent stains. This thesis has also pioneered the first in vivo research relating to the iron cylinder in the model organism, zebrafish, and findings indicate a large therapeutic window over which the cylinder can bring about its effects.

[发布机构] University:University of Birmingham;Department:School of Chemistry

[关键词] R Medicine;RC Internal medicine;RC0254 Neoplasms. Tumors. Oncology (including Cancer)