How bursting microbubbles can help reduce tumours

9 Oct 2018

Prof John Callan. Image: TechWatch

The idea of a bubble bursting is traditionally a negative one, but not in this case. TechWatch’s Emily McDaid finds out how SonoTarg’s microbubble technology can help increase the efficacy of pancreatic cancer drugs.

No cancer is a ‘good’ cancer, but some are worse than others. Pancreatic cancer tends to be asymptomatic until the tumour is large and established, and surgery often isn’t an option. Chemotherapies are administered through the bloodstream but it’s estimated that only 1pc of the drug may get to the actual tumour.

Researchers at Ulster University have dedicated their careers to creating SonoTarg, which could be a new lease of life for patients with this deadly disease.

A simplistic way of explaining SonoTarg is that it uses microbubbles that burst when they’re activated by ultrasound technology. By putting chemotherapy drugs in these microbubbles, they can target the exact location of the pancreatic tumour, applying ultrasound to the patient’s abdomen and releasing the drugs with pinpointed accuracy.

Co-founder Prof John Callan explained why this is important: “Pancreatic cancer has atrocious survival rates; a mere 5pc of patients will be alive five years after diagnosis. Only 20pc of patients are eligible for surgery, which is currently the only hope of a cure.”

One of the other challenges with pancreatic tumours is that there’s a very dense protective coating (a stromal barrier) around the tumour. This tissue acts like a shield, preventing drugs from getting in.

animation of green microbubble showing presence of oxygen.

Schematic of the microbubble. Image: SonoTarg

In addition to using their microbubbles to zero in on the tumour with conventional chemotherapy drugs, the researchers have also incorporated a completely new sonodynamic treatment. Callan explained: “This involves the activation of an otherwise harmless drug that has no effect on the body. But, when it comes into contact with ultrasound, it converts normal oxygen we breathe into a highly reactive form of oxygen that kills cells – in this case, cancer cells.”

Using their ultrasonic-activated microbubbles with the double hit of two cancer-killing drugs is “much more effective than chemo alone”, said Callan.

The microbubbles are 100 times smaller than the diameter of a human hair. Luckily, they are used in medicine already for ultrasound imaging. This is important because it means the company – which will eventually be a spin-out from Ulster University – is already on a path to getting the therapy approved for use in humans. This could shave years off the approval process.

Callan said: “We’ve reformulated the microbubbles. We discovered that if you increase the pressure on the bubble, but still at very safe levels of ultrasound, it will burst.” This process, delivering drugs using ultrasound-induced cavitation – is an example of precision medicine. An animation on SonoTarg’s website depicts the process visually.

Callan explained the two main benefits:

  1. More of the drug goes straight to the tumour rather than other healthy parts of the body, reducing side effects
  2. When the bubble bursts, the critical processes that drive that event help carry the drug deeper into the tumour tissue

When could this be brought to market? Callan said: “We have conducted lab-based preclinical testing. We’ve demonstrated that this works in a lab setting. The next step is for us to show that this works in human patients and that it’s safe.”

He goes on: “All of the bits have been used safely in humans before, we’ve just packaged them differently. If all the ducks fall in a row, we’d intend to be at that point towards the end of next year or the beginning of 2020.” He cautioned, however: “We still have some development work to do before then.”

It’s hard for me to imagine how researchers manipulate organic materials that small. I ask, what sort of technical work is ongoing now? He said: “We’re optimising the manufacturing process to produce bubbles with batch-to-batch reproducibility.”

Callan tells me that he hopes the manufacturing process would take place in Northern Ireland, at least “initially, for the trial”.

SonoTarg has five co-founders, three academics and two practising doctors. The team has been developing the therapy for “six or seven years now, at least”, Callan said.

Will there be an opportunity for investors? “We have some investors who seem quite keen. We’ve taken some development funding from Invest NI as well,” Callan said.

By Emily McDaid, editor, TechWatch

A version of this article originally appeared on TechWatch

SonoTarg is a finalist in the annual Invent competition run by Connect at Catalyst Inc, aiming to showcase the best and brightest innovators that Northern Ireland has to offer. Invent 2018 will take place on Thursday 11 October in Belfast, where 12 finalists will battle it out for a £33,000 prize fund.

TechWatch by Catalyst covered tech developments in Northern Ireland