Semi-autonomous non-invasive surgery: The "outside in" of molecular-targeted theranostics for cancer

The aim of this fellowship is to bring together a multi-disciplinary team of experts in Engineering, Physics and Medicine, with support from two industrial partners. This team will develop a revolutionary new system to improve both diagnosis and therapy (theranostics) of head and neck cancers. The treatment and long-term aftercare of patients with head and neck cancers represents an unmet clinical need due to the debilitating side-effects of current invasive treatments, such as damage to the vocal cords. The proposed system will use semi-autonomous robotics to combine high intensity focused ultrasound (HIFU) with laser illumination. The proposed strategy will also capitalise on recent advances in precision medicine - the tailoring of medical care to the specific requirements of the individual patient.
Nano-scale metallic particles may be manufactured in such a way that they will target and attach to cancerous tissue. Once in the correct location, it is possible to activate them for both diagnostic and therapeutic purposes. When simultaneously exposed to ultrasound and laser illumination (of nanosecond duration), tiny vapour bubbles form around the nanoparticles. When these bubbles burst, they emit a clear ultrasound signal which can be detected via conventional diagnostic ultrasound systems. This ultrasound signal is only emitted in the presence of the unique combination of nanoparticles, laser illumination and ultrasound. This approach provides direct localisation of cancerous regions and has greater sensitivity compared with current photoacoustic imaging.
HIFU therapy is a non-invasive and non-ionising technique which is already in clinical use for the treatment of various malignancies including prostate and liver cancer. This fellowship seeks to enhance the use of HIFU for the treatment of head and neck cancers since the presence of these vapour bubbles created by the targeted nanoparticles is known to enhance thermal damage in a localised region and improve treatment efficacy.
Integrating this theranostic approach with a waterproof robotic arm, developed in conjunction with a UK-based robotics manufacturer, will allow for semi-autonomous cancer treatment, which will remove the need for highly trained surgical teams and result in reduced treatment costs for the NHS. A waterproof system enables the entire imaging/surgical apparatus to be submerged in a water tank to allow patients to comfortably lie prone on the treatment bed without the need for direct physical contact with the theranostic system.
This ambitious three-year fellowship comprises three key research objectives. The first objective is the development of a theranostics system combining a diagnostic and therapeutic ultrasound system and a laser light delivery method. The second objective, supported through a collaboration with a biomedical imaging company (iThera Medical), is the validation of the targeting and safety of the gold nanoparticles in cell lines and in animal models, followed by demonstration of the efficacy of this theranostic technique in pre-clinical models of head and neck cancer. The final research objective is the development and validation of semi-autonomous waterproof robotics with the capability of identifying and treating cancerous regions with minimal input from an operator.
This multi-disciplinary approach could be rapidly translated into clinical applications. This would provide an answer to a currently unmet clinical need for the treatment and long-term management of patients with head and neck cancers. In addition, the use of targeted therapies in conjunction with semi-autonomous robotic systems represents a revolutionary new future for healthcare, where highly skilled, long and expensive surgical procedures could be replaced with a safer, less invasive, lower cost alternative.

Impact from this fellowship will be realised over short (3-5 years), medium (5-10 years) and long-term (10-20 years) time scales. The short-term beneficiaries will include both project partners: ST Robotics and iThera Medical. A waterproof robotic arm would be a new product line for ST Robotics, which will allow them to target different markets such as non-destructive testing with ultrasound. For iThera, we would be an earlier adopter of their new imaging modality, and the first to use it for imaging gold nanoparticles at this wavelength. Thus, this collaboration would help develop this technology, and promote its capabilities to the wider research community.
Precision nanomedicine in conjunction with robotic systems is a new concept in the public consciousness. Through the outreach activities and non-specialist website described in the pathway to impact (PtI4), awareness and understanding of this novel approach to cancer identification and treatment will be increased. This would provide patient benefit to those with head and neck cancers as it demonstrates considerable effort is underway to improve future patient outcomes. Furthermore, as these newer less invasive treatments become available they will provide an option for existing patients should they suffer future recurrence. This is especially true of patients who have previously had a significant radiation dose from radiotherapy, in whom the further use of radiation is limited.
Cetuximab is commonly used for treating cancers in the bowel and head and neck, typically in conjunction with chemotherapy or radiotherapy, and it also has potential for treatment of other malignancies such as lung cancer. Thus, Cetuximab-functionalised nanoparticles (PtI2) have the potential to improve treatments for numerous cancers in the medium-term. The main beneficiaries of this are clinicians and cancer patients. For example, our industrial partner, iThera Medical, would use these nanoparticles as contrast agents in conjunction with their clinical imaging system. Production of these particles would be licensed to the UK's National Biologics Manufacturing Centre, providing benefit and value to the UK taxpayer. With the development of a clinical prototype (PtI1), commercialisation options will be reviewed in conjunction with the University's Commercialisation team. For a project of this type, this would likely be a licensing arrangement with a company who already have expertise in the market or a spinout company, benefiting this company or venture capital investors.
This fellowship will lead the way in developing a new approach to the management and treatment of cancer. The long-term impact of this research would be the implementation of semi-autonomous surgical robotic systems that could be used in specialist centres, creating a new approach for the treatment and management of cancers. Once the system enters clinical use, impact would be realised in the form of a reduced co-morbidity for patients and lower treatment costs. As this is a non-invasive and non-ionising technique it ensures rapid recovery of patients irrespective of age, a dramatic reduction in the need for medical intervention and no long-term side-effects. Since there are no long-term side effects associated with high intensity focused ultrasound exposures, when compared with surgical intervention, radiotherapy or chemotherapy, patients would maintain a higher quality of life, thus overcoming a significant unmet clinical need with current head and neck cancer treatments. There are more than ten thousand new cases annually of head and neck cancers in the UK, and post-operative costs in the first year exceed £19k. These costs mainly result from side effects from the invasive procedures used in treatments. Thus, this new technique would reduce overall costs to the NHS, ultimately benefiting the UK taxpayer.