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Novel Self-assembled Nanoligand Drug Carriers as Blood – Brain – Barrier Therapeutics

By 24th November 2019January 29th, 2020No Comments

The following study was conducted by Scientists from Chinese Academy of Sciences; University of Copenhagen, Denmark; Newcastle University, UK; Danish Cancer Society Research Center, Copenhagen, Denmark; S. M. Discovery Group Inc USA; S. M. Discovery Group Ltd., Durham, UK.

Scientists developed a novel “Brain-specific phage-derived peptide” noted as NanoLigand Carriers, NLCs that are specifically engineered to cross the blood-brain-barrier. Study is published in Nature Communications as detailed below.

Nature Communications 10, Article number: 4635 (2019)

Crossing the blood-brain-barrier with nanoligand drug carriers self-assembled from a phage display peptide


The filamentous bacteriophage fd bind 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 recognise 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 transferrin receptor and the receptor for advanced glycation-end products, cross the blood-brain-barrier and reach neurons and microglial cells. Through intravenous delivery of NLC-β-secretase 1 (BACE1) siRNA complexes we show effective BACE1 down-regulation in the brain without toxicity and inflammation. Therefore, NLCs act as safe multifunctional nanocarriers, overcome efficacy and specificity limitations in active targeting with nanoparticles bearing phage display peptides or cell-penetrating peptides and expand the receptor repertoire of the display peptide.


Nature Communications.



Wu, L., Ahmadvand, D., Su, J. et al. Crossing the blood-brain-barrier with nanoligand drug carriers self-assembled from a phage display peptide. Nat Commun 10, 4635 (2019) doi:10.1038/s41467-019-12554-2.