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Women to Watch: engineered bubbles as a drug delivery tool with Eleanor Stride

Written by Eleanor Stride

engineered bubbles

Magnets, bubbles and ultrasound – what do they have in common? They are all being used as exciting new methods to deliver drugs.

In this interview, we speak with Eleanor Stride (University of Oxford, UK) to find out about the application of engineered bubbles in oncology, including her work investigating whether engineered bubbles can induce an immune response.

How do current drug administration methods for cancer contribute to adverse side effects?

The majority of chemotherapy drugs are administered orally or intravenously, i.e. in the form of a pill or an injection. Consequently, they are transported throughout the body, with only a very small fraction (<1%) being absorbed at the target site(s). The rest of the drug is taken up in healthy tissue, inevitably leading to side effects.

How are you using bubbles to overcome drug delivery challenges?

Bubbles offer several useful features for drug delivery. They have been used as contrast agents for ultrasound imaging for several decades because they are so responsive to changes in pressure. We use that responsiveness to control when and where a drug gets delivered. The bubbles consist of a gas core surrounded by a biocompatible shell. We encapsulate drugs within the shell so they are temporarily deactivated. Once the bubbles are at the target site, we use a high-energy ultrasound pulse to destroy the bubbles and release the drug. The motion of the bubble when we hit it with ultrasound also helps to “pump” the drug into the tissue. This is very important when tumors have a poor blood supply. The bubble motion also helps to permeabilize cancer cell membranes to further increase drug uptake. Because the bubbles are such good contrast agents, we can track them in the bloodstream with low-energy ultrasound pulses to make sure they’re reaching the target. We are also currently investigating some of the chemical processes that occur in the core of the oscillating bubble to see if these can usefully contribute to the anti-tumor effect and potentially be used as a means of activating drugs to reduce the risk of side effects even further. 

What components do you add to the bubbles to ensure they reach the site of the tumor?

We can attach other materials to the shell such as molecules that make the bubbles “sticky” to tumor blood vessels. We can also incorporate magnetic nanoparticles, which enable us to concentrate the bubbles in the tumor using a magnetic field applied outside the body before releasing the drug in order to maximize the dose.

What types of cancer are engineered bubbles particularly useful for?

Drug delivery is particularly challenging in large solid tumors, e.g. pancreatic adenocarcinoma, and so we have been focusing our efforts on these. The only type of cancer for which bubbles will likely not be useful is lung cancer, this is because it is very difficult to safely focus ultrasound in the lungs due to the presence of gas there. Lung ultrasound is however being used increasingly as a diagnostic technique so potentially bubbles could be used in some cases. The skull also presents a challenge, but there have been some very promising clinical trials using bubbles for the treatment of glioblastoma and we have a project on treating secondary brain tumors that is also showing promise.

Could you discuss your most recent work investigating whether engineered bubbles can induce an immune response and whether this could be applied as a therapeutic option for cancer?

One of the challenges with the use of bubbles, and indeed most physical therapies, is that they can only be used to treat individual tumors. In late-stage cancer where there are multiple (metastatic) tumors, it is usually not possible to detect and treat every site. Similarly, if a tumor has a very poor blood supply, it is impossible to get a sufficient number of bubbles into the target area to be effective. We have recently published some results that we’re very excited about showing that by treating one tumor with bubbles and ultrasound, we can stimulate an immune response which causes other tumors to also shrink [1]. This could enable a much wider application of bubbles and ultrasound for the treatment of late-stage cancers. We are now working to understand the underpinning mechanisms and how we can optimize the treatment protocol.

Interviewee profile:

I’m Eleanor Stride, I’m a Professor of Biomedical Engineering at the University of Oxford (UK). I did my undergraduate degree and PhD in Mechanical Engineering at University College London (UK), followed by a Royal Academy of Engineering and EPSRC Research Fellowship. I moved to Oxford in 2011 to join the Biomedical Ultrasonics, Biopharmaceuticals and Biotherapy Group (BUBBL) and became a full Professor in 2014. I am now leading a team working jointly between Engineering and Medicine.

The opinions expressed in this interview are those of the author and do not necessarily reflect the views of Oncology Central or Future Science Group.