Investigations into New Chemical Toolkits for Drug Delivery, Sensing and Cellular Imaging Applications using the Fluorescence Labelling of Biomolecule

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As healthcare and technology advances lead to longer life expectancies, an ever increasing and ageing populationfaces a growing risk from non-communicable diseases such as cancer. The development of novel, targetedpersonalised sensing and imaging drugs is highly desirable. This research would address cleaner, rapid syntheticprocesses with pharmaceutical relevance by the utilisation of inexpensive protocols and drugs currently underdevelopment for clinical trials, e.g. immune-therapeutics. The work would be fully embedded in the strategic researchdirection of biosensing and imaging/healthcare technology, which could have real impact in early diagnosis of cancerand personalised medicine. The PhD thesis will focus on the general area of biosensing, imagining and therapeuticinnovations for cancer diagnosis and therapy.OutlineThe project would largely be based on enhancing the understanding of the fundamental interactions betweenluminescent probes and targeting biomolecules such as synthetic peptides upon conjugation, leading to a biologicalprobe, which could potentially target living cancer cells under controlled microenvironments. A secondary aim wouldbe to gain an in depth understanding of the synthetic and analytical chemistry underpinning the chemistry implicatedin the antibody labelling or tagging with small fluorescent molecules.We would design, synthesise, and characterise new metal complexes as "all-in-one" imaging probes, centred oncertain antibodies of interest for clinical trials of cancer, such as Avastin or anti-EGFR. Outputs would lead toimproved sensing and bioimaging probes for early cancer diagnosis, including for hypoxic tumours, which arecurrently hard to access for imaging or treatment. This could advance our fundamental understanding of theassociated conjugation chemistry in aqueous environments, including using bioorthogonal and supramolecularassembly protocols, thus allowing for correlation between antibody behaviour post conju gation and its kineticstability, with the metal ions present in the molecular appendages and their speciation in aqueous media.Project Aimsa) Functionalisation of biomolecules of interest for immune-therapies such as simple synthetic peptides, onto metalbound imaging probes.b) Understanding how fluorescent metal complexes can be incorporated in multimodality (PET/optical) probes, whichare then anchored onto antibodies without destroying the fragile biomolecular constructs.c) Labelling of biomolecules with model species of relevance to PET/SPECT metallic radio isotopes such as 68Gaand 89Zr. Development and testing protocols for the "cold" chelation of Zn(II), Ga(III) and Zr(IV) ions in water.Dr Charareh Pourzand (20 %) will assist in this project by providing knowledge and training in tissue and cell culture.This will allow for the imaging probes designed to be tested within cells.Professor Andy Burrows (10 %) will act as a mentor and will also support in the more chemical aspects of this project