Penetrating the blood brain barrier

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Normally the blood brain barrier ensures that the sensitive brain is able to function without risky interferences from the rest of the body. However, this is a problem if you want to treat brain diseases like Alzheimer’s, schizophrenia or cancer, as all therapeutic drugs are kept away extremely effectively. This is the challenge researchers from DTU Nanotech are aiming to solve.

Major progress with sophisticated tumour targeted multifunctional nanoparticles may potentially offer a new and improved platform for medical diagnostics, therapeutics or ‘theranostics’ of glioma.

Malignant glioma represents the most frequently diagnosed type of malignant brain cancer. The current way of treating this type of brain cancer consists of a combination of surgical resection, radiotherapy and chemotherapy. “Unfortunately, however, because of the invasive nature of malignant glioma, prospects of a complete recovery are not good. Furthermore, there is a high probability of incurable reoccurrence, which may be ascribed to the current insufficient treatment platform”, says Martin Bak, postdoc at DTU Nanotech.

The brain endothelium cells – which form the blood brain barrier – prevent the transport of drugs across the barrier. Additionally a wide range of active membrane efflux pumps present in the barrier also ensures the regulation of any such penetration.

Numerous strategies have been employed in the attempt to cross the blood brain barrier. To put the difficulty of brain drug development into perspective, not a single large biologic drug was approved by the US Food and Drug Administration (FDA) in 2016, if one only looks at the drugs that have an effect beyond the blood brain barrier. Consequently, there is an ever-growing need for new treatments of brain diseases not least because of the increasing lifespan of western populations.

Gold nanoparticles as a diagnostic tool.

By using specific surface modifications such as certain polymers, proteins or antibodies, it is possible to optimise the blood circulation and its specificity towards a given cell subtype, such as cells in brain tumour tissue.

“We have synthesised uniform gold nanoparticles and created a tailor-made surface modification platform that can facilitate the desired blood circulation,” says Martin Bak. “Utilising multiple specially engineered antibodies, which have been tuned to have various affinities towards a given target in the brain, it has been possible to target a specific brain receptor. This has facilitated the penetration of our gold nanoparticles across the blood brain barrier and far into the brain tissue”, Martin Bak explains.

A combination of nanoparticles and e.g. a therapeutic drug or a diagnostic marker may potentially solve issues about solubility, stability and accumulation of a given drug or marker that would otherwise be impossible to use and translocate them through the blood brain barrier into the brain tissue to elicit their effect. Increasing the accumulation of our nanoparticles into the brain will allow improved delivery of the encapsulated therapeutics, thus lowering the therapeutic doses needed to achieve the desired effect.

Currently, we have multiple papers ready for publication on the subject and we expect to translate our findings into drug-carrying nanoparticles within the year to target specific brain cancer models. Essentially it is a mechanistic study but will hopefully result in an improved targeting strategy for the entire CBIO-group’s diagnostic, therapeutic or theranostic nanocarriers. Potentially creating a better treatment for glioma patients.

Source: DTU

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