Pioneering study by Danish researchers reveals how tiny “medicine transporters” can be delivered to the brain
In time, the technique will make it possible to deliver drugs across the blood-brain barrier, enabling targeted therapies for brain disorders.
If a patient has a brain disease, such as a tumour, it would be useful to be able to bombard the specific area with medicine yet avoid hitting and affecting other parts of the brain.
However, there is an issue that needs to be addressed before we reach this stage – how to pass the blood-brain barrier.
This barrier is a selectively permeable membrane whose job is to ensure a consistent biochemical environment in the brains of humans and other mammals, thus preventing the great majority of substances from passing into the brain via the bloodstream.
The matter has puzzled scientists for decades. In trial after trial, they were forced to conclude that the blood-brain barrier is a seemingly invincible opponent.
However, a Danish team of researchers has now demonstrated that it is possible to sneak through the barrier with the help of a kind of “medicine transporter”.
These medicine transporters – each only a hundred millionth of a millimetre in size – are actually specially engineered, spherical fat particles. And because they are hollow, they can transport goods – such as medicines.
‘We are the first to prove that it’s actually possible to transport drugs across the barrier and deliver them into the brain via the bloodstream. Our findings are the result of seven years of work in partnership with a long list of Danish researchers. We’re thrilled that we’ve succeeded,’ says Professor Martin Lauritzen from Rigshospitalet and the Department of Neuroscience, University of Copenhagen, who headed the project.
Experiments with mice gave answers
But how can we prove that a nano-sized transporter – in this case, a medicine transporter – actually penetrates the blood-brain barrier?
Basically, the answer is by monitoring traffic:
Using a special technique – two-photon imaging – researchers were able to track the driving patterns of the medicine transporters in a number of mouse models. Exactly like video cameras along our roads record traffic flow.
The researchers injected nanoparticles – the tiny medicine transporters – with fluorescent markers into the bloodstreams of the mice. With the help of the colours, Professor Lauritzen and his colleagues were able to track the particles under the two-photon microscope and see how they behaved when they reached the blood-brain barrier.
‘In principle, if you can put a dye into a nanoparticle, you can put anything into it, even a drug. This is how we know that our technique will be able to be used for medical therapies,’ says Professor Lauritzen.
However, an application using microscopic medicine transporters in this way is not imminent.
Professor Lauritzen explains that, although mice and humans are both mammals and both have a blood-brain barrier, a lot more experiments will be needed before the technique can be tested in humans:
‘We’ll have to conduct trials on monkeys first. If this works, it will probably also work on humans.’
The explanation is extremely complex, but put in layman’s terms:
- The nanoparticles, engineered by experts at the Technical University of Denmark (DTU), have an antibody on their outer surface.
- This antibody is directed at a protein that clings to the inner surface of the blood vessels in the brain – and, thus, to the actual blood-brain barrier.
- When the antibody encounters the protein, the nanoparticle binds to the protein.
- The nanoparticle is then “spat” into the brain, passing the blood-brain barrier.
The discovery was made by researchers from the University of Copenhagen (UCPH), the Technical University of Denmark (DTU), Aalborg University (AAU) and Rigshospitalet, University of Copenhagen.
The project was largely funded by a Lundbeck Foundation grant, and the description of the tiny medicine transporters was recently published in a research article in the scientific journal Nature Communications.