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Transport of Engineered Nanomaterials across the blood-brain-barrier

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How nanoparticles enter – and impact – the brain

Understanding how some nanomaterials can cross the blood-brain barrier, and the effects they have, is important for environmental protection and novel treatments.

Health

Thanks to the blood-brain barrier (BBB), the human brain is a well-protected organ. Working like a forcefield around the brain, the BBB keeps potentially dangerous toxins and pathogens out while letting vital nutrients in. But while the BBB is extremely good at what it does – it isn’t perfect. “There is evidence that air pollution-derived nanomaterials can be found in human brains in highly polluted urban environments,” says Éva Valsami-Jones, a professor of Environmental Nanoscience at the University of Birmingham. “The big question is how these nanomaterials are able to cross the blood-brain barrier.” Coordinated by Valsami-Jones and led by Zhiling Guo, a Marie Skłodowska-Curie individual fellow, the EU-funded NanoBBB project investigated how nanomaterials enter the brain through the BBB and the impact this has on the human body.

An imperfect shield

Using a number of advanced scanning and X-ray techniques, the team tested a range of metal and metal oxide nanomaterials of various sizes, shapes and compositions. “By providing extraordinary resolution of very complex, small-scale processes, these techniques let us observe the behaviour of nanomaterials across the blood-brain barrier in detail,” remarks Guo. Using an artificial BBB that she constructed in the lab, Guo found that silver and zinc oxide, two nanomaterials widely used in everyday consumer and healthcare products, are particularly well-suited to crossing the BBB. “Due to their unique physiochemical properties, these materials were able to transform and cross the model barrier in the form of particles or dissolved ions,” explains Guo. The team then compiled their findings into a unique database on nanomaterial transport and chemical transformation. “This information is critical for assessing the safety of products that use these types of nanomaterials,” adds Valsami-Jones. “It will also play a vital role in the development of future biomedical applications of nanomaterials.” Guo is currently working to upload the complete data set to a repository of nano safety data. Once done, it will be fully available for use by other researchers.

Risks and rewards

The NanoBBB project succeeded in providing important new insights into how nanomaterials can cross the BBB. “Not only can this information be used to help protect the brain from potentially dangerous nanomaterials, it opens the door to designing nano-enabled formulas capable of delivering targeted drug therapies to the brain,” says Guo. “Furthermore, our work allows for the development of computer simulations for predicting nanomaterial uptake, transformation and transport across the blood-brain barrier,” notes Valsami-Jones. Researchers plan to seek additional funding to conduct in vivo experiments on a wider range of nanomaterials, and compare the permeability of other biological barriers.

Keywords

NanoBBB, nanomaterials, brain, blood-brain barrier, BBB, air pollution, X-ray, biomedical, drug therapies

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