Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
GLOBETECH PUBLISHING LLC
GLOBETECH MEDIA

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

By BiotechDaily International staff writers
Posted on 18 Jun 2014
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.

Related Links:

Mayo Clinic



Channels

Drug Discovery

view channel
Image: Wafers like the one shown here are used to create “organ-on-a-chip” devices to model human tissue (Photo courtesy of Dr. Anurag Mathur, University of California, Berkeley).

Human Heart-on-a-Chip Cultures May Replace Animal Models for Drug Development and Safety Screening

Human heart cells growing in an easily monitored silicon chip culture system may one day replace animal-based model systems for drug development and safety screening. Drug discovery and development... Read more

Biochemistry

view channel
Image:  Model depiction of a novel cellular mechanism by which regulation of cryptochromes Cry1 and Cry2 enables coordination of a protective transcriptional response to DNA damage caused by genotoxic stress (Photo courtesy of the journal eLife, March 2015, Papp SJ, Huber AL, et al.).

Two Proteins Critical for Circadian Cycles Protect Cells from Mutations

Scientists have discovered that two proteins critical for maintaining healthy day-night cycles also have an unexpected role in DNA repair and protecting cells against genetic mutations that could lead... Read more

Business

view channel

“Softer” Mass Spec Techniques Gain Advantage in Biomarker Discovery

Two mass spectrometry (MS) technologies, MALDI and DESI, are increasing in applications as their effectiveness is established, according to Kalorama Information (New York, NY, USA) in its report “Proteomics Markets for Research and IVD Applications (Mass Spectrometry, Chromatography, Microarrays, Electrophoresis, Immunoassays,... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.