Nanotech ‘passport to the brain’ for therapeutics

Researchers discover a new nanotech approach to deliver therapies through the blood-brain barrier.

Scientists at Tufts University have discovered a way to deliver therapeutics safely through the blood-brain barrier in a nanotech breakthrough that could pave the way for treatment delivery for neurological disorders such as Alzheimer’s Disease or brain damage caused by stroke.

Longevity.Technology: the blood-brain barrier (BBB) protects the brain from toxins and bacteria that could otherwise cause brain infections, while still allowing vital nutrients to get in: it has proven remarkably efficient at its job.

However, the BBB has also created one of the biggest challenges in medicine – how can you get therapeutics for neurodegenerative disorders to the brain safely and effectively through this protective barrier?

A team of biomedical engineers from the Tufts University School of Engineering in Massachusetts has found a solution [1]. They have developed tiny lipid-based nanoparticles featuring neurotransmitters to help carry drugs, large molecules and gene editing proteins across the BBB. Their innovation has been proven to work in the brains of mice, and further research is now needed to discover whether this delivery method could work in the human brain. 


 

“… we can deliver a wide range of molecules by packing them into the lipid-based nanoparticles … [and] also achieve delivery across the blood-brain barrier without disrupting the integrity of the barrier …”

 


 

It is hoped the discovery could provide a “passport to the brain” in order to surmount current constraints experienced when trying to take therapeutics into the central nervous system. This could open up a huge array of opportunities to use treatments which would otherwise be impossible to get to the brain. 

Neurodegenerative disorders, as well as brain tumours and strokes, affect millions of people globally, with Alzheimer’s Disease and Parkinson’s disproportionately affecting the elderly and leading to a loss of quality of life for many as they age. This latest discovery may eventually pave the way for the delivery of new treatments. 

It builds on previous bodies of work including research at Denali Therapeutics in San Francisco where scientists used modified human antibodies to access the brain through Transferrin receptors. Meanwhile, an Israeli team has overcome the BBB with a nanochip that carries a neurodegenerative “neural growth factor”.

Qiaobing Xu, Associate Professor of Biomedical Engineering at Tufts University explained their approach: “The power of our method is that it is extremely versatile and relatively non-disruptive. We can deliver a wide range of molecules by packing them into the lipid-based nanoparticles without chemically modifying the drugs themselves. We can also achieve delivery across the blood-brain barrier without disrupting the integrity of the barrier.”

Currently, the treatment of neurodegenerative disorders, brain tumours, infections and stroke has been limited in part by the problems in safely delivering drugs and macromolecules into the brain without risk. Direct injection can cause potential infection or tissue damage, while the use of carriers such as modified viruses and nanoparticles, nanocapsules and polymers can be costly or complex. 

In the latest study, authors took advantage of the fact that certain neurotransmitters have the chemical “passport” needed to gain access to the brain. They attached a lipid molecule to the neurotransmitter so that the resulting NT-lipidoid could be doped into lipid nanoparticles (LNPs). These tiny bubbles of liquid can then encapsulate therapeutic drugs and can be injected intravenously in order to carry the drugs through the BBB. The NT-lipidoid then takes over and helps to take the LNPs across the barrier so they can interact and fuse with neurons and brain cells to deliver therapies.

Using this method, researchers were successfully able to deliver a small-molecule anti-fungal drug into the brain as well as the gene editing protein GFP-Cre and macromolecules including a Tau antisense oligonucleotide, which has been found to inhibit the production of tau protein which is connected to Alzheimer’s disease. 

Although further research and clinical trials are needed to confirm the safety and efficacy of the delivery method, it is hoped this will lead to a significant breakthrough for central nervous system drug delivery. 

Feihe Ma, a post-doctoral scholar in the Xu lab at Tufts said the system was “simple, effective and potentially broadly applicable,” while Liu Yan, graduate student at the Xu lab added: “We envision that a wide range of neurological therapeutics could eventually be tried that were previously thought to be impractical due to limitations in delivery.” 

[1] https://advances.sciencemag.org/content/6/30/eabb4429

 

Carla Heyworth
Carla is sub editor at Longevity.Technology and she's the glue that keeps the team on track and the articles rolling-out. She has an extensive background in B2B communications, events and marketing. Carla's a visual person and can often be found behind a camera or editing photos

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