Making Waves – and Microbubbles
Boosting the efficacy of cancer drugs with sonoporation
William Aryitey |
The use of ultrasound to increase cell membrane permeability – sonoporation – is a fast-growing avenue of investigation (1), (2). Here, sonoporation expert Spiros Kotopoulis gives us a rapid rundown of this emerging field.
Tell us about your research.
My work at the University Hospital of Bergen in Norway primarily focuses on the therapeutic use of ultrasound and microbubbles to deliver chemotherapy drugs. We started with simply simulating bubble behavior in different situations, and moved on to studying the relationship between microbubbles, ultrasound, and drug uptake. Using high-speed microscopy, we can visualize the interaction at frame rates of up to several million frames per second. We put bubbles and cells in a culture chamber under a microscope, and apply the ultrasound, to force the microbubbles into the cells. The culmination of that work so far was a clinical trial showing that chemotherapy in conjunction with sonoporation nearly doubled the median survival time in pancreatic cancer patients, with no added side effects, compared with chemotherapy alone (1).
Is the technique restricted to cancer applications?
From disrupting the blood–brain barrier (so drugs can cross it) to increasing the rate at which bone fractures heal, there are numerous potential medical applications. The benefit of sonoporation is that you can get more of a drug into a specific location.
Ultrasound scanners are a common and easily-accessible tool – why hasn’t there been more focus on sonoporation?
I think the answer is simply that there haven’t been many large-scale human trials of sonoporation in action. If larger international clinical trials confirm the results from smaller trials like ours, I think it will quickly become much more widespread. Study into sonoporation is relatively recent, so research has been pretty limited. But there does seem to be an exponential increase every year, with more and more people entering the field and bigger conferences dedicated to therapeutic ultrasound.
A fantastic place to witness the growth and diversity of therapeutic ultrasound is the biannual Acoustical Society of America meeting. There are many labs working on an array of applications at the meeting, but the main bulk of the research can be split into two broad categories; high-energy ultrasound, where you burn or heat tissue, and low-energy ultrasound (sonoporation), where you make membranes more permeable to molecules. To me, both sides are very interesting and show a lot of promise, so I’m hopeful that they will develop in parallel.
What makes this an exciting field to work in?
Sonoporation is a multidisciplinary, divergent field. My background is that of an engineering physicist, and in my lab there are biologists, chemists, pharmacists, and more – all working to reach a common goal. Sonoporation may have started as physicists playing with cells, or biologists playing with ultrasound, but the increasing emphasis on translational research in science today has helped to bring us together into a distinct field.
I believe the future of sonoporation is bright. I’m optimistic that its growth will continue, and ultimately improve patients’ quality of life and survival.
- Kotopoulus et al., “Sonoporation-enhanced chemotherapy significantly reduces primary tumour burden in an orthotopic pancreatic cancer xenograft”, Mol Imaging Biol, 16, 53-62 (2014). PMID: 23877869.
- Helfield et al., “Biophysical insight into mechanisms of sonoporation”, Proc Natl Acad Sci U S A, [Epub ahead of print] (2016). PMID: 27551081.