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2020-06-05 - Article/Dans un journal avec peer-review - Anglais - 30 page(s) (Soumise)

Andre Séverine , Larbanoix Lionel , Verteneuil Sébastien, Stanicki Dimitri , Nonclercq Denis , Vander Elst Luce , Laurent Sophie , Muller Robert , Burtea Carmen , "Development of an LDL receptor-targeted peptide susceptible to facilitate the brain access of diagnostic or therapeutic agents" in Biology

  • Edition : Multidisciplinary Digital Publishing Institute (MDPI) (Switzerland)
  • Codes CREF : Histologie (DI3212), Résonance magnétique nucléaire (biophysique) (DI131B), Sciences biomédicales (DI3200), Biochimie pharmaceutique (DI3491), Biologie moléculaire (DI3111), Neuropathologie (DI332C), Pharmacocinétique (DI3431), Chimie organique (DI1313), Imagerie médicale, radiologie, tomographie (DI3243), Biologie cellulaire (DI311D)
  • Unités de recherche UMONS : Chimie générale, organique et biomédicale (M108), Histologie (M118)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé), Institut des Biosciences (Biosciences)
  • Centres UMONS : Centre de Recherche en Microscopie et Imagerie Médicale (CMMI)
Texte intégral :

Abstract(s) :

(Anglais) Blood-brain barrier (BBB) crossing and brain penetration are really challenging for the delivery of therapeutic agents and imaging probes. The development of new crossing strategies is needed and a wide range of strategies (invasive or not) have been proposed so far. The receptor-mediated transcytosis is an attractive mechanism allowing the non-invasive penetration of the BBB. Among available targets, the LDL receptor (LDLR) shows favorable characteristics mainly because of the lysosome-bypassed pathway of LDL delivery to the brain, allowing an intact discharge of the carried ligand to the brain targets. The phage display technology was employed to identify a dodecapeptide targeted to the extracellular domain of LDLR (ED-LDLR). This peptide is able to bind the ED-LDLR in the presence of natural ligands and dissociates at acidic pH and in the absence of calcium, in a similar manner as the LDL. In vitro, our peptide is endocytosed by endothelial cells by the caveolae-dependent pathway, preventing its degradation and suggesting its transcytosis. The in vivo studies performed by Magnetic Resonance Imaging and Fluorescent Lifetime Imaging suggest the brain penetration of this ED-LDLR-targeted peptide.


Mots-clés :
  • (Anglais) blood-brain barrier
  • (Anglais) LDL receptor
  • (Anglais) receptor-mediated transcytosis
  • (Anglais) peptide
  • (Anglais) phage display