Conjugated polymer nanoparticles for fluorescence-guided intraoperative tumour visualization

Every year there are 900,000 new cases of head and neck cancer (HNC) worldwide. Unfortunately, the number of people being diagnosed and dying of this disease in Liverpool is significantly higher than the rest of England, and in some deprived areas, higher than parts of India and South Africa. The most rapidly increasing type of HNC is of the oropharynx (tonsils and back of the tongue).

New surgical approaches allow us to perform resections through the mouth, with minimal side effects for the patient compared to traditional open surgery. However, the positive or close margin rate following this trans-oral approach is very high (>80%). There is an urgent clinical need for a feasible and accurate method to intraoperatively identify tumour margins and allow accurate resection.

The technology for realising the potential of fluorescence-guided surgery (FGS) exists; in 2010, Intuitive Surgical (Sunnyvale,CA) introduced an imaging module called Firefly (available within LUHFT) that is able to ‘see’ the organic dye indocyanine green (ICG) in the near-infrared (NIR) spectrum, that collects preferentially in a tumour. However, this type of imaging demonstrates low spatial resolution, poor penetration depth and too much background noise

Conjugated Polymer Nanoparticles are a unique and novel form of molecular bioimaging probes with a high degree of photostability, highly specific targeting and powerful magnetism. They are modifiable to produce distinct optical properties with bright emission. Furthermore, the demonstrate outstanding photo, thermo and chemical stability. Together with the ability to enhance their tumour specificity, these probes therefore offer the potential to overcome many of the limitations that have hampered image-guided surgery.

Clinical impact/Bench-to-bedside

This project will enable us to develop and optimise a new class of polymer probes, with proven efficacy on an established and ‘in-use’ robotic imaging system; this ‘reverse-engineering’ approach of using an established clinical system helps to ensure functional relevance. This has the potential to transform not only trans-oral surgery, but all surgical oncology procedures that that would benefit from enhanced tumour visualization. As well as the clinical impact, side-by-side correlation with histopathological assessment will provide valuable translational observations on the interactions between these polymers and cancer/normal cells to significantly advance our understanding of nanoparticle biology.  

Methods

The successful candidate will work in a team comprising both academic surgeons and experienced surface chemists to readily translate advances into translational relevance. Methods will include but are not limited to:

1)      Preparation and optimisation of Conjugated polymer nanoparticles

2)      Characterisation of polymers

   Including: UV-Vis spectroscopy (absorption properties), fluorimetry (emission properties and lifetime measurements); Transmission Electrotonic Spectroscopy (particle size and shape), Dynamic Light Scattering

3)      In vitro and explant testing on the surgical robotic Firefly imaging system

The successful candidate could come from either a clinical academic background or nanomedical/surface chemistry background. The project would be ideally suited to a PhD, although other postgraduate degrees of shorter duration e.g. MPhil, MD, would be considered on candidate preference. Clinically qualified applicants would be appointed on an honorary research contract only with Liverpool University Hospitals NHS Foundation Trust to facilitate translational work.