Supervisors: Prof Sir Alfred Cuschieri and Dr Mike MacDonald
Whole body 3D scanning techniques are crucial for the detection of solid tumours. However, these imaging techniques reveal intrinsic low sensitivity. In the last decades, the progress in engineering molecular tools for active targeting has led to the development of highly selective molecules able to recognise a specific antigen with affinity comparable with the one of monoclonal antibodies (mAb). Among these molecular tools, molecularly imprinted polymers (MIPs) stand out. MIPs are also called “plastic antibodies” due to their affinity for the target, moreover they present several advantages over the mAb, particularly their resistance to the most of the solvents and high temperatures and the low cost production. The possibility to produce nano-sized MIPs conjugated to fluorescent agents (i.e. fluorescent monomers or quantum dots) makes these polymers suitable candidates for nanomedicine applications.
Thus, the aim of the project is to synthesise a multifunctional composite nanomaterial which couples the recognition properties of MIPs to a fluorescence agent, for in vivo imaging of cancer.
At the beginning of the project, the idea was to embed opportunely functionalised far-red emitting quantum dots (QDs) onto the MIPs during the polymerisation against the selected target molecule (i.e. hVEGF epitope). These experiments were carried out at IMSaT lab (University of Dundee, UK) and at the Biotechnology lab (University of Leicester, UK), under the supervision of Prof Piletsky. Although the polymerisation resulted in the embedding of QDs onto the imprinted polymer, the process did not allow the production of fluorescent QD-MIP nanoparticles, obtained either in organics or in water solution. An alternative approach was thus carried out to address this problem, by which thiol-stabilised far-red emitting QDs were covalently attached onto the surface of the MIPs after the polymerisation.
These QD-MIP nanoparticles were characterised in terms of their absorbance at 197nm, for the evaluation of the yield of the reaction, size and fluorescence. In essence, these studies show the production of 60-170nm QD-MIPs imprinted against hVEGF epitopes, epi1 and epi2.
Fluorescent MIPs imprinted against epi1 synthesised in PBS were also produced by exploiting a fluorescein-based monomer.
Affinity measurements were performed to assess the Kd of the QD-MIPs for the target. Preliminary results indicate dissociation constants between 1.4-1.8nM.
Journal and Conference Papers and Posters
[April 2017] Targeted in vivo fluorescent imaging of tumour overexpressing human vascular endothelial growth factor by hybrid ‘plastic antibodies’. PhD Thesis submitted April 2017.
[March 2017] In vivo recognition of human vascular endothelial growth factor by molecularly imprinted polymers. Cecchini, A., Raffa, V., Canfarotta, F., Signore, G., Piletsky, S., MacDonald, M.P. an Cuschieri, A. Nano Letters, 14 (4), 2307-2312
[September 2016] MIPs coupled to quantum dots as tools for the detection of tumour angiogenesis in zebrafish. Poster presented at PHOTON16, Leeds, UK, 5th September 2016.
[August 2016] MIPs coupled to quantum dots as tools for the detection of tumour angiogenesis in zebrafish. Poster presented at the Biophotonic approaches: From molecules to living systems conference, Dundee, Scotland, 23rd August 2016.
[June 2016] MIPs coupled to quantum dots as tools for the detection of tumour angiogenesis in zebrafish. Poster presented at MIP2016, the 9th International Conference on Molecular Imprinting, Lund, Sweden, 29th June 2016.
[April 2016] Fluorescent “Plastic Antibodies” as Nanotools for Cancer Imaging in Zebrafish. Paper presented at 7th International Congress, Nanotechnology in Medicine & Biology, 7th April 2016, Krems, Austria.
[June 2015] Shedding light on cancer: novel hybrid nanomaterial for in vivo imaging. Poster presented at PHOTONEX Scotland, Glasgow, UK, 3rd June 2015.
[April 2015] Plastic antibodies as innovative tool for cancer imaging. Poster presented at BioNanoMed2015, 6th International Congress, Nanotechnology in Medicine & Biology, 15th April 2015, Graz, Austria.