Charting the course across the blood-brain barrier
David Nathanson, Paul S. Mischel
David Nathanson, Paul S. Mischel
Published December 22, 2010
Citation Information: J Clin Invest. 2011;121(1):31-33. https://doi.org/10.1172/JCI45758.
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Commentary

Charting the course across the blood-brain barrier

Abstract

The blood-brain barrier (BBB) presents a significant obstacle to delivery of targeted therapies to brain tumors. In this issue of the JCI, Staquicini and colleagues apply an in vivo phage-displayed library of random peptides to identify differentially expressed peptides that can be used to transport targeted agents across the intact BBB. The authors uncover a non-canonical, peptide-mediated iron-mimicry mechanism to induce transport of the transferrin/transferrin receptor complex across the BBB. They then demonstrate the ability of phage-targeting approaches to deliver therapeutic cargo and molecular imaging reporters across the BBB in an intracranial glioblastoma mouse model.

Authors

David Nathanson, Paul S. Mischel

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Figure 1

Peptide-mediated iron mimicry transports the transferrin/TfR complex across the BBB, delivering therapeutic and imaging cargo.

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Peptide-mediated iron mimicry transports the transferrin/TfR complex acr...
The BBB is composed of a variety of cells, including endothelial cells with tight junctions, pericytes, perivascular neurons, and astrocytes. Under normal conditions, the BBB prevents the passage of small molecules into the brain. Receptor-mediated transport allows passage of selected molecules across the BBB. The binding of iron to transferrin induces a conformational shift from the open form of transferrin (Apo-Tf) to the closed form (Halo-Tf), facilitating transport of bound iron-transferrin in complex with TfR across the BBB. The iron peptide mimic CRTIGPSVC specifically binds Tf, enabling transport of the peptide and its cargo in complex with transferrin/TfR across the BBB.