Transport characteristics of a novel peptide platform for CNS therapeutics

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DOIResolve DOI: http://doi.org/10.1111/j.1582-4934.2009.00930.x
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TypeArticle
Journal titleJournal of Cellular and Molecular Medicine
Volume14
Issue12
Pages28272839; # of pages: 13
Subjectblood-brain barrier; therapeutics; drug delivery; Angiopeps; low-density lipoprotein receptor-related protein-1; receptor-mediated transcytosis; brain disease
AbstractNew and effective therapeutics that cross the blood-brain barrier (BBB) are critically needed for treatment of many brain diseases. We characterize here a novel drug development platform that is broadly applicable for the development of new therapeutics with increased brain penetration. The platform is based on the Angiopep-2 peptide, a sequence derived from ligands that bind to low-density lipoprotein receptor-related protein-1 (LRP-1), a receptor expressed on the BBB. Fluorescent imaging studies of a Cy5.5Angiopep-2 conjugate and immunohistochemical studies of injected Angiopep-2 in mice demonstrated efficient transport across the BBB into brain parenchyma and subsequent co-localization with the neuronal nuclei-selective marker NeuN and the glial marker glial fibrillary acidic protein (GFAP). Uptake of [¹²⁵I]-Angiopep-2 into brain endothelial cells occurred by a saturable mechanism involving LRP-1. The primary sequence and charge of Angiopep-2 were crucial for its passage across the BBB. Overall, the results demonstrate the significant potential of this platform for the development of novel neurotherapeutics.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); NRC Institute for Biological Sciences
Peer reviewedYes
NPARC number15336778
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Record identifier1029ec3d-7122-4a70-ad67-54d6072ebb9b
Record created2010-05-21
Record modified2016-05-09
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