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Nanoparticles Designed to Cross Blood-Brain Barrier

Neurons

(commonfund.nih.gov)

11 Oct. 2019. Nanoscale particles derived from viruses are shown in tests with lab mice to cross the blood-brain barrier, and reach nerve cells in the brain. An international team led by researchers at Newcastle University in the U.K. describe the technique in today’s issue of the journal Nature Communications.

The blood-brain barrier acts as a safety measure to protect the brain from foreign substances crossing from the blood stream while allowing nutrients to flow through. Blood vessels in the brain form a support network for brain functions, with tightly-packed cells lining blood vessels. This barrier also keeps out drugs to treat neurological conditions, such as Parkinson’s or Alzheimer’s disease, and its impaired functioning is also implicated in these disorders. So far, no efficient method is available to penetrate this barrier, preventing some 98 percent of current drugs from reaching the brain or central nervous system.

Researchers led by Moein Moghimi, professor of pharmaceutics and nanomedicine at Newcastle’s pharmacy school, are seeking safe, simple, and reliable techniques for delivering drugs across the blood-brain barrier. The team’s technology is based on bacteriophages, viruses that infect and replicate inside bacteria, with some of these viruses already known to efficiently target brain cells.

The researchers sought to emulate those properties with a synthetic bacteriophage-like particle. The particle contains peptides, short chains of amino acids from bacteriophages, screened in advance for their activity in brain cells, with one peptide meeting many of the desired characteristics. And the team — with participants from China, Iran, Denmark, and the U.K. — designed the nanoscale particle with a hierarchical peptide structure that they hypothesized would better bind with target cells. Those targets are cells lining blood vessels in the brain, from which the particles could cross into brain cells.

To prove the concept, Moghimi and colleagues configured their nanoscale particles to deliver a form of gene therapy to brain cells of lab mice. The therapy in this case targets the BACE1 enzyme in brain cells, associated with Alzheimer’s disease. The researchers added small interfering RNA to the nanoparticles, designed to limit expression of aberrant genes producing the BACE1 enzyme, which were injected into the mice.

The results show mice receiving the nanoparticles have lower BACE1 production in their brains. In addition, the mice show no evidence of toxicity or inflammation, suggesting that this delivery method could be safe for crossing the blood-brain barrier in patients.

In a Newcastle University statement, Moghimi calls the findings a breakthrough that “allows for minimally invasive combination delivery through an intravenous injection of various drugs, peptides, and nucleic acid therapeutics to the brain.” He adds, “We have a long way to go, but we hope that our technology platform may open up many opportunities to address neurodegenerative diseases with modern therapeutics and genetic drugs.”

Moghimi and co-author Shadi Farhangrazi co-founded the company S. M. Discovery Group with offices in Durham, U.K. and Denver, Colorado. S. M. Discovery Group develops nanoscale mechanisms for delivery of drugs and diagnostic agents. Farhangrazi is the company’s CEO, while Moghimi is a scientific adviser.

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