Nano-submarines for drug delivery - Protein

Nano-submarines for drug delivery
21-05-2007
Thijs Westerbeek
Radio Netherlands
War-submarines that travel through our bodies looking for alien invaders; molecular battle ships that know exactly where to find a specific infection. Once they've arrived they get out their guns and start firing at exactly the right moment and in exactly the right amount. Sounds like science fiction? Well, maybe not for much longer, because this is (allowing for some artistic freedom) precisely what two young Dutch scientists, Dr Willeke Daamen and Master of Science Paul Geutjes have come up with.

Dr Daamen en Mr Geutjes work at the department of biochemistry of the University Medical Centre St. Radboud in Nijmegen. Almost by accident they discovered the natural process which produces 'biocapsules' . These capsules are minute hollow globules, which can carry any substance, also toxic ones, until it can safely be released at the location where it can perform its task. The discovery was a matter of serendipity; the scientists regularly freeze all kinds of proteins at extremely low temperatures for experiments. It was during one of those experiments that they saw a strange thing happening....

The recipe
Mr Geutjes explains the process that resulted after careful and painstaking observations:
"We dissolve, for instance, a protein, and then very quickly freeze the solution down to 200 degrees below zero. Inside the ice the protein then rearranges itself into strings, we call them sheets. Next we slowly heat up the whole concoction to minus 20 degrees, mind you; its still frozen. At this temperature we allow it to 'stew' for a while. During this phase the protein strings slowly turn into little balls. After that we extract all the moisture by 'freeze-drying' it and then the balls turn into hollow globules. Done! And all this just happens naturally; it's almost like making cheese...'

But what about liposomes?
In itself the concept of hiding active ingredients inside minute hollow globules isn't entirely new. Liposomes - often used in cosmetics - work in the same way. These hollow balls of fat are so small they can penetrate the skin and carry their - hopefully - beneficial content inside. But the range of applications for liposomes is limited and they are difficult to produce. The simple fact that the 'Nijmegen biocapsules' sort of just 'happen' is a big plus. But there is more, as Willeke Daamen explains:
"Our biocapsules can be made from many different things. Protein, our preferred organic building material, can be broken down in the body after the job is done; nothing harmful remains. What's more; since our globules can be organic, we can very easily 'build in' antibodies that are specific to certain diseases. Let me give you an example: A patient has cancer of the pancreas, hence antibodies against this specific tumour are to be found in his blood. The drug against cancer of the pancreas is toxic, like most cancer medication."

"If we wrap this drug in our biocapsules and equip them with the patients own antibodies, the capsules will act as if they were antibodies themselves; once injected into the body they will 'home in' to the sick pancreas, all the while keeping the dangerous drug hidden inside. Upon arrival they will release the drug in sufficient amounts to be effective, but because this is very local, the patient will suffer from far less side effects..'
Paul Geutjes continues:
'And even this release of the drug in question can be controlled: Every illness, including cancer of the pancreas, produces it's own enzymes which remain concentrated at the affected area. Since our biocapsules can be made from almost anything, we can choose a protein that will be dissolved by this enzyme alone!'
Virtual magic bullet
It seems the Nijmegen scientists have stumbled upon a virtual magic bullet, but sadly a lot of work remains to be done. Until now the capsules are produced and tested 'in vitro', in the lab, and under those conditions they perform beautifully. The process is patented and available to other scientists to use in their own research. The use in patients however is another story altogether. Animal testing is about to begin and only after that will the first clinical trials begin. Willeke Daamen:
'It will take ten years at least before this technique can become common practice in the hospital, but we're very hopeful. Meanwhile anybody who has ideas about interesting uses for our biocapsules is welcome to get into contact....'
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