Bubbles, ultrasound and radiotherapy: creating a new approach to drug delivery

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Using funding from the CRUK–EPSRC Multidisciplinary Project Award, a team of researchers from the University of Oxford are sharing their respective expertise to unlock exciting new approaches in chemotherapy and radiotherapy using ultrasound.

A work environment that inspires collaboration

Working at the University of Oxford, clinical oncologist Dr Anne Kiltie, biomedical engineer Professor Eleanor Stride and biophysicist Professor Boris Vojnovic found the close proximity of their different departments enabled them to identify clinical challenges which their combined expertise could tackle. Eleanor describes how the multidisciplinary environment provided the catalyst for their project, which was funded by a Multidisciplinary Project Award.

We’re extremely fortunate to be working in a building where different types of scientists share the same facilities. Our project came about as the result of a conversation over coffee about using advanced fluorescence microscopy to characterise microbubbles.

The team are using their unique combination of skills to explore ways to improve the effectiveness of chemoradiation in bladder cancer, by minimising the systemic toxic effects produced when radiotherapy is used in parallel with chemotherapy. The side effects are difficult to manage in older patients, creating an urgent clinical need which this multidisciplinary project could help to address.

The collaboration: bringing together medicine, biology, chemistry, physics and engineering

The team will explore how to target chemotherapy drugs by encapsulating them in microbubbles and delivering them through direct injection or via circulation in the bloodstream. To release the drug, while preventing it from affecting nearby healthy tissue, the team will use high-intensity ultrasound waves to burst the bubbles near the tumour.

The drugs are designed to enhance the effects of radiotherapy, however current techniques for targeting radiotherapy rely upon a computerised tomography-based imaging system which has limited resolution. To address this second challenge, the team are instead using three-dimensional ultrasound to guide the radiotherapy which simultaneously controls microbubble drug delivery.

The complex nature of the challenge they’ve set themselves demands a careful integration of the range of skills and expertise that each of the team can provide.

This type of project just wouldn’t be possible without having the right combination of medicine, biology, chemistry, physics and engineering, so everyone on the team has a really important part to play.

Prof Eleanor Stride

If the proof of principle is demonstrated in this work, the team will develop the method for testing in a phase 1 clinical trial for bladder cancer.

Learning how to share knowledge across disciplines

Even though the team knew from an early stage that their very distinct disciplines could complement each other in order to explore a new approach to drug delivery, the development of their idea needed to evolve over further meetings and by circulating information from their respective fields to each other.

Eleanor describes how the team first tackled the language barrier between the disciplines, which then allowed them to effectively combine their research.

The main challenge was first getting to grips with the terminology and practicalities of the different techniques we’re putting together. The microbubbles I’d previously developed weren’t compatible with radiotherapy so we had to reformulate the chemical composition. We’ve had to do a fair amount of lateral thinking to address this and similar issues but that’s part of the fun.

Committee perspective: complementary expertise and exciting technology

The committee that reviewed the team’s proposal were very enthusiastic about the project. They felt that the sophisticated ultrasound technique, used to both trigger drug release and improve targeting of radiation therapy, was an exciting technology and that the translation of these techniques into preclinical models was an important step. They also highlighted the complementary expertise that Anne’s experience in bladder cancer models and Eleanor’s experience in ultrasound-guided microbubble therapeutics brought to the project.