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Details of Grant 

EPSRC Reference: EP/X01374X/1
Title: Translational nanoconstructs for targeted tissue accumulation and guided surgery in cancer
Principal Investigator: Redshaw, Professor C
Other Investigators:
Prior, Dr TJ Archibald, Professor S
Researcher Co-Investigators:
Project Partners:
Hull Univ Teaching Hospitals NHS Trust Lightpoint Medical Ltd Southern Scientific
Stream Bio Ltd
Department: Chemistry
Organisation: University of Hull
Scheme: Standard Research
Starts: 01 January 2023 Ends: 31 December 2025 Value (£): 572,613
EPSRC Research Topic Classifications:
Chemical Synthetic Methodology Materials Synthesis & Growth
Medical Imaging
EPSRC Industrial Sector Classifications:
Healthcare
Related Grants:
EP/X013677/1 EP/X014495/1
Panel History:
Panel DatePanel NameOutcome
27 Sep 2022 Healthcare Technologies Investigator Led Panel Sept 2022 Announced
Summary on Grant Application Form
This project aims to deliver transformative advances in the development of nanoparticle constructs for use in precision surgery and beyond (e.g. therapeutic drug delivery). This will be achieved by bringing together experts with complimentary expertise in calixarene chemistry, nanochemistry, PET (positron emission tomography) imaging and surgical imaging.

By developing the chemistry of calixarenes, we will optimize the galectin receptor binding affinity and demonstrate selective cancer cell targeting. Our preliminary studies reveal that radiolabelled (18F) 'Clicked' calixarenes are readily accessible, with improved HPLC purification (achieved via guest incorporation), which enables in vivo bio-distribution, highlighting ideal (renal) clearance.

A major benefit of employing a calixarene-based scaffold is the ability for further functionalization. With this in mind, using standard protocols (Click chemistry), the calixarene will be further modified with the addition of a NOTA motif. The incorporation of such a strongly binding motif will allow us to develop the radiolabelling of this new platform technology, with maximum flexibility i.e. with both 18F and 68Ga radionuclides.

The functionalized calixarene scaffold will be immobilized on luminescent conjugated polymer nanoparticles to enhance the imaging capabilities. The biodistribution and tumour uptake of the delivery platform will then be accessed (PET imaging), and results will be fed back into the synthetic programme to allow us to optimize the results. Following successful in vitro studies, in vivo tumour uptake will be assessed; tumour and organ uptake will be quantified to assess biodistribution and tumour targeting.

The final phase of the project will explore opportunities for using this technology for the collection of spectra in vivo, by combining with a customizable dual camera head. To evaluate depth sensitivity and multimodal guidance an endoscopic gamma probe will be used for multi-functional probe identification. Such a combined approach will be suitable for pre-clinical imaging with a focus on high resolution and signal quality.
Key Findings
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Potential use in non-academic contexts
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Summary
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Organisation Website: http://www.hull.ac.uk