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There is no debate about the importance of the brain. Because of its complexity, it is still a central challenge to gain access and deliver therapeutics over the blood-brain barrier into the brain for the treatment of tumors or neurodegenerative diseases. But have researchers currently broken through and pioneered the possibility to overcome this barrier?

The blood–brain barrier is a protective layer that separates the central nervous system from the systemic circulation throughout the rest of the body. It consists of multiple closely connected cells. This protection is necessary since the body is exposed to many components that can interfere with the homeostasis of our most sensitive organ.

However, this protection also has its disadvantages making drug-delivery of a therapeutically relevant dosage into e.g. brain tumors extremely difficult. On top of that, Sara points out that “the current therapeutic strategies have some serious physical and chemical constraints,” making them deficient up until today.

Sara Pompe, who is a PhD student at the Utrecht ľ�ϸ���Ӱ��, is developing an approach for a targeted drug delivery into the brain and subsequently in tumors. The pathway she is taking is very promising to deliver drugs over the blood-brain barrier with minimal harmful side effects.

Her approach is based on the use of nanobodies. Nanobodies are small functional parts of antibodies which are normally used by the body’s immune system to fight pathogens. Because of their smaller size, ease of production and modification, nanobodies are perfect to be used in the context of drug innovation. 

First, a protein specific nanobody-drug complex is designed. Then, the construct is administered to the body detecting a specific receptor-protein that is highly expressed on the cell surface of the blood-brain barrier. Sara: “It is a suitable target for drug delivery into the brain, since it doesn’t interfere with the natural delivery of nutrients which are essential for proper brain functioning”.

Nanobody-based drug delivery has a very high relevance in medicine since the nanobody might be universally applied to be coupled with any kind of therapeutic, which is aimed to have its mode of action in the brain.

When looking at future perspectives of nanobody-based drug delivery, one could say it is more than just suitable. Sara: “It has a very high relevance in medicine since the nanobody might be universally applied to be coupled with any kind of therapeutic, which is aimed to have its mode of action in the brain”.  In addition, the construct can be modified by coupling it to a fluorescent labelling agent, which would allow a precise localization of the tumor tissue via imaging for an image-guided surgery. In the end, it seems that novel approaches like Sara’s can bring us yet one step closer to overcome this barrier.