Most drugs, genetic materials, and other therapeutic agents are very difficult to use inside the brain because of the blood-brain barrier. There have been attempts to use ultrasound and microbubbles to create temporary passages through the barrier, including as a possible therapy for Alzheimer’s disease, but this is approach is not easy or ideal.
Now, researchers from Newcastle University in the U.K. have used a peptide (chain of amino acids) to create drug-loaded nanoparticles, about the size of viruses, that can autonomously cross the blood-brain barrier.
The new particles can be loaded with nucleic acid-based therapies, the kind that are already in development, as well as drugs, peptides, imaging agents, and other compounds. Not only do the new nanoparticles cross the blood-brain barrier, they can also protect their cargo, which would otherwise not be able to survive the journey to the target tissue.
To make the new nanoparticles, the Newcastle team used a peptide component of a virus that can enter the brain, called filamentous bacteriophage fd. They slightly changed it to suit their needs and, by adding water to it, were able to form their nanoparticles.
Testing these on mice, they showed that the nanoparticles successfully crossed the blood-brain barrier and were able to get near neural and microglia cells in the brain. Initial testing showed no obvious toxicity, so there’s hope that the new particles will soon help to deliver new therapies for brain disorders.
From the study abstract in Nature Communications:
The filamentous bacteriophage fd binds a cell target with exquisite specificity through its few copies of display peptides, whereas nanoparticles functionalized with hundreds to thousands of synthetically generated phage display peptides exhibit variable and often-weak target binding. We hypothesise that some phage peptides in a hierarchical structure rather than in monomeric form recognize and bind their target. Here we show hierarchial forms of a brain-specific phage-derived peptide (herein as NanoLigand Carriers, NLCs) target cerebral endothelial cells through the transferrin receptor and the receptor for advanced glycation-end products, cross the blood-brain-barrier and reach neurons and microglial cells.
Study in Nature Communications: Crossing the blood-brain-barrier with nanoligand drug carriers self-assembled from a phage display peptide
Via: Newcastle University