HIFU treatment: Targeted drugs at a nano-scale

Pharmaceutical scientist Gert Storm works on the design, research and testing of targeted nanomedicines. These are tiny balls that can be transported to the right place in the body, helping doctors to dose medicine more efficiently and preventing the drug from damaging other parts of the body. "A drug that combats kidney problems should not end up at the lungs."

If you have a headache, you take paracetamol or ibuprofen. After about twenty minutes, your headache will start to subside and it will eventually disappear. But how does a painkiller know that the pain is in your head? And can we control that?

Porous vessel

Professor G. Storm

"A drug enters your bloodstream via an injection or pill," explains biopharmacist Gert Storm. "Let's first make a distinction between a drug and its active substance. The active substance, also known as an active pharmaceutical ingredient (API), the pharmacologically active drug molecule, is the substance that needs to cure us. The drug or medicine is the entire drink, pill or injection."

"The interior of a blood vessel is lined with cells that make the vessel wall almost entirely non-porous, but a local infection can make the vessel lining a little bit more porous in that area," says Storm. " However, the drug does not 'know' where to go and only ends up at the right place in only low amounts because our heart pumps blood through our body. Chances are small that the API will eventually end up at the right place. And the substance also tends to leave the body quickly, in urine for instance, so that we have often to start off with a high dosage that is administered frequently.

More efficient dosing

Such intensive dosing schedules are especially unfortunate for medicine as they can lead to severe side effects. So Storm and his colleagues conduct research into Drug Targeting. "We want to guide the drugs to the right 'address' in the body, thereby making high dosages redundant and increasing the efficacy of the medicine without burdening the body parts which do not need it," he explains. " We are developing medicines that go straight to the source of the problem, where they need to work." One way to do that is to exploit the more porous vessel walls which are often present in diseased areas.

Exploding nanoballs

Storm explains that they work with tiny (‘nano’) balls made of fats or polymers. "We put the API into the balls. There are already fat globules present in our body and are therefore a natural way to transport substances" he explains. "A nanoball will be able to go through the porous vessel wall and is less likely to end up in urine than the API itself"

Storm works at the UMC one day a week. "We work with temperature-sensitive nanomedicines, which are globules that burst open at a specific temperature and then completely release the drug in seconds. We mainly use them to combat tumours. In an MRI scanner, we can identify the precise location of a tumour. We then use ultrasound to heat the tumour to 42°C, which is exactly the temperature at which the globules are triggered to burst open. The API is delivered at the right place in the right way, and high dosages indusing side effects are therefore not needed. Other organs, which may be susceptible to the substance, will not be damaged either, as the ultrasound waves are really focussed on the tumour area only."

Full integration

"Right now, we are mainly conducting such ‘triggered drug release’ research with the aim to treat tumours. I think that in the near future we will also be able to expand this technique to other symptoms, such as chronic inflammation and other conditions that are easy to reach with ultrasound. And although we still have to overcome some hurdles, I believe that this treatment method can become a clinical reality within a very short time frame. The first clinical study in breast cancer patients is expected to start this year."

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