Jack Pearce

Doctoral Researcher
Physical Sciences of Imaging in the Biomedical Sciences CDT 

Thesis project - "Using chitosan nanoparticles for the therapeutic imaging of tumour vessels"

Supervisors:
Professor Zoe Pikramenou, School of Chemistry
Professor Roy Bicknell, Institute of Cardiovascular Sciences
Dr Hamid Dehghani, School of Computer Science

Nanoparticle or nanoscale molecules have gained increasing traction in cancer research due to the possibility of drug and imaging probe conjugation. Conjugating drugs and probes to nanoscale particles drastically increases the number of molecules targeted at each cell. Nanoscale particles can also be targeted at specific cell proteins through the conjugation of antibodies or aptamers.

The project will study the selective targeting of chitosan nanoparticles in tumours using optical imaging. New nanoparticle agents coated with monoclonal antibodies and siRNA will be prepared. Antibodies allow for targeted delivery of molecules to specific cells within an organism. siRNA gives us the ability to silence specific genes in the cells targeted by the antibodies. We will entrap siRNA and imaging probes within the chitosan nanoparticles. Chitosan nanoparticles will be used to develop a theranostic imaging tool and to deliver siRNA to tumour blood vessels. Routes to deliver siRNA on nanoparticles to tumour vessels to silence pro-angiogenic gene expression will be explored. I will focus on CLEC14A, an endothelial membrane protein. C-type lectin domain family 14 member A(CLEC14A) is a transmembrane protein that is a confirmed regulator of endothelial cell migration and blood vessel sprouting.

Effects on tumour growth and the vasculature will be characterised with the IVIS machine and other confocal fluorescence microscopies when tissues are examined. The project involves new probes, development of biomedical studies and different optical imaging techniques. IVIS will utilise the luciferase activity transfected into the 4T1 breast cancer cells and can be used to calculate the primary tumour size and locate metastasis. H&E sections staining will be used to assess changes the number and volume of tumour vessels after treatment with siRNA therapies.