Physical Sciences of Imaging in the Biomedical Sciences CDT
Thesis project - "Multimodal nano-theranostic systems targeting tumour biomarkers"
Professor Michael Hannon, School of Chemistry
Professor Zoe Pikramenou, School of Chemistry
Dr Nik Hodges, School of Biosciences
Dr Hamid Dehghani, School of Computer Science
New theranostic nanoparticles (based on cores such as gold or silica) will be designed that are co-coated with: (i) a fluorescent imaging label (ii) a targeting vector for the cells to be imaged (ii) (iii) a therapeutic agent active against the cell type. The approach has the potential to be extended to incorporate MRI active agents and probes in other modalities too. A variety of luminescent d- and f-block metal complexes will be investigated as lumophores along with organic dyes. As therapeutics a range of metallo-agents will also explored including Pt(IV) prodrugs. Targetting vectors will include folates and alternative biomarkers of potential interest. Folate receptors are over expressed on the surface of many cancer cells and tissues, and are an acknowledged cancer biomarker.
Once the synthetic routes are established and a range of nanoparticles are available, these theranostic nanoparticles will be studied alone and in culture with cells with and without suitable receptors for the targeting unit (eg folate receptor positive and negative). The uptake into, movement within and the effects upon the different cell types will be assessed and related back to the design features of the nanoparticles so as to optimise these theranostic designs. Techniques of study will include Imaging by Fluorescence Microscopy of the luminescent probes; TEM / Confocal Microscopy of gold nanoparticles; Fluorescence Assisted Cell Sorting (FACS) analysis of the distribution of the theranostic nanoparticles amongst cancer cells. Computational analysis of imaging data will be used to compare across modalitites and to enable particle tracking.