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Imaging Chemistry and Biology (pre-2019)

Functionalised nanoparticles for theranostics

Project ID: 2016_215

Student: Hannah Perry

1st supervisor: James Wilton-Ely, Imperial College London
2nd supervisor: Rene Botnar, King’s College London

The project will focus on the development of nanoparticles and nanorods with mixed surface units for use in a combined imaging and therapeutic application (‘theranostics’). Modular modification of the nanostructure surface will allow units responsible for targeting, real-time magnetic resonance imaging (MRI) and cytotoxicity to be incorporated within the same assembly. The pathway to these materials will lead to new methodology combinations for functionalising nanoparticles and deliver targeted (and hence lower dose) imaging agents.

In vivo, gold nanoparticles accumulate at tumour sites which typically display immature vasculature with wider fenestrations than normal mature blood vessels. For these reasons, nanoparticles are increasingly being employed in cancer therapy. However, this project aims to achieve an additional degree of targeting using aptamers. These are short strands of oligonucleotides or peptides which can be chosen for their strong affinity for specific proteins. Nanoparticles and nanorods bearing these aptamers have been shown to result in very specific protein binding, bringing the nanostructure into the proximity of the target protein.

Through the modular functionalisation of the nanostructure surface with aptamers, cytotoxic metal units and an imaging modality, it is proposed that real-time imaging of the tumour site and the subsequent therapeutic action will result. This will be achieved either by photoexcitation (laser light) of the metal unit or photothermal excitation (near-IR laser) of the gold nanostructure, or both. Through the choice of aptamers specific for proteins associated with cancerous cells, aptamer-coated gold nanostructures will be prepared which also carry a ‘payload’ of therapeutic and imaging units. Metal surface units will be selected on the basis of their cytotoxicity and imaging (MRI) properties. The combination of targeting features, MRI and switchable (photoexcitation) metal-based therapy will pave the way for their use in theranostics.

This multidisciplinary project will develop skills in coordination chemistry, ligand synthesis, nanomaterials synthesis, magnetic resonance imaging and cell culture. It is not expected that the student will have prior experience in all areas but some background in synthesis will be an advantage.

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