Surgeons operating on cancer patients currently rely on visual inspection and touch to decide where to cut, often missing microscopic tumour edges. This project builds nanoparticles that latch onto cancer cells and glow under special cameras, making malignant tissue visible in real time during surgery. The problem is that current surgical guidance tools cannot reliably distinguish cancer from healthy tissue at the microscopic level. This leads to incomplete tumour removal or unnecessary removal of healthy tissue. The researchers are developing calixarene molecules—cup-shaped chemical structures—that bind to galectin receptors overexpressed on cancer cells. These molecules are then attached to luminescent polymer nanoparticles and labelled with radioactive tracers for PET imaging. If successful, the technology would give surgeons a dual-mode imaging system: a camera head that sees the glowing nanoparticles on the tumour surface, and an endoscopic gamma probe that detects deeper deposits. This could reduce the need for repeat surgeries and improve patient outcomes by ensuring complete tumour resection in a single operation. The project is primarily fundamental chemistry and preclinical imaging development. Similar work on targeted nanoparticles has already transformed how surgeons approach brain and prostate tumours, and this calixarene-based platform could extend that precision to a wider range of cancers.
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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.
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