Biotin and glutathione targeting of solid nanoparticles to cross human brain endothelial cells

Szilvia Veszelka, Mária Mészáros, Lóránd Kiss, Zoltán Kóta, Tibor Páli, Zsófia Hoyk, Zsolt Bozsó, Lívia Fülöp, András Tóth, Gábor Rákhely, Mária A. Deli

Research output: Article

7 Citations (Scopus)


The blood-brain barrier restricts drug penetration to the central nervous system. Targeted nanocarriers are new potential tools to increase the brain entry of drugs. Ligands of endogenous transporters of the blood-brain barrier can be used as targeting vectors for brain delivery of nanoparticles. Objective: We tested biotin-labeled solid nanoparticles for the first time and compared to biotinylated glutathione- labeled nanoparticles in brain endothelial cells. Method: Neutravidin coated fluorescent polystyrene nanoparticles were derivatized with biotin and biotinylated glutathione. As a human in vitro blood-brain barrier model hCMEC/D3 brain endothelial cells were used. Cell viability by MTT test, uptake and transfer of the nanoparticles across the endothelial monolayers were measured. The uptake of the nanoparticles was visualized by confocal microscopy. Results: The tested nanoparticles caused no change in cell viability. The uptake of biotin- and glutathione-labeled nanoparticles by brain endothelial cells was time-dependent and significantly higher compared to non-labeled nanoparticles. The penetration of the glutathione-labeled nanoparticles across the endothelial monolayer was higher than the biotin-targeted ones. Biotin- and glutathione-targeted nanoparticles were visualized in hCMEC/D3 cells. We verified that hCMEC/D3 express mRNA for sodium-dependent multivitamin transporter (SMVT/SLC5A6) responsible for the blood-brain barrier transport of biotin. Conclusion: Biotin as a ligand increased the uptake and the transfer of nanoparticles across brain endothelial cells. Biotinylated glutathione could further increase nanoparticle permeability through endothelial monolayers supporting its use as a brain targeting vector.

Original languageEnglish
Pages (from-to)4198-4205
Number of pages8
JournalCurrent pharmaceutical design
Issue number28
Publication statusPublished - aug. 1 2017

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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