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Synthetic Peptide Non-Covalently Transports Cancer Drugs Across the Blood-Brain Barrier

By BiotechDaily International staff writers
Posted on 18 Jun 2014
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Cancer researchers have used a novel synthetic peptide to transport chemotherapeutic compounds and other small molecules across the blood-brain barrier and into the brains of mice.

The transport peptide, K16ApoE, comprised sixteen lysine residues and 20 amino acids corresponding to the LDLR (low density lipoprotein receptor)-binding domain of apolipoprotein E (ApoE). Investigators at the Mayo Clinic (Rochester, MN, USA) had demonstrated previously that by mimicking a ligand-receptor system, K16ApoE could deliver three different proteins (beta-galactosidase, IgG, and IgM) in a non-covalent fashion across the blood-brain barrier. To their knowledge this was the first report demonstrating successful delivery of various proteins across the blood-brain barrier that did not involve chemically linking the proteins with a carrier entity.

In the current study, the investigators delivered chemotherapeutics and other agents into the brains of mice either by injecting the carrier peptide and the drugs separately or as a mixture via the femoral vein. A modification of the method comprised injection of K16ApoE pre-mixed with cetuximab, followed by injection of a small-molecule drug.

The investigators reported in the May 21, 2014, online edition of the journal PLOS ONE that seven-of-seven different small molecules were successfully delivered to the brain via K16ApoE. Depending on the injection method, brain uptake was 34–50-fold greater for cisplatin and 54–92-fold greater for methotrexate with K16ApoE than without. Visually intense brain-uptake of the dyes Evans Blue, Light Green SF, and Crocein scarlet was also achieved. Direct intracranial injection of Evans Blue showed locally restricted distribution of the dye in the brain, whereas K16ApoE-mediated intravenous injection resulted in the distribution of the dye throughout the brain.

"We know that some chemotherapeutic agents can kill brain tumor cells when they are outside the brain (as in a laboratory test). But because the agents cannot cross the blood-brain barrier, they are not able to kill brain tumor cells inside the brain. With the peptide carrier, these agents can now get into the brain and potentially kill the tumor cells," said senior author Dr. Robert Jenkins a neurology researcher at the Mayo Clinic.

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