Cited by 118Nanoparticle-Based Drug DeliveryBarrier Structure and Function StudiesAdvanced Drug Delivery Systems

Systemically Administered Brain-Targeted Nanoparticles Transport Peptides across the Blood—Brain Barrier and Provide Neuroprotection

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Yemisci, Muge, Caban, Secil, Gursoy-Ozdemir, Yasemin, Lule, Sevda, Novoa-Carballal, Ramon, Riguera, Ricardo, Fernandez-Megia, Eduardo, Andrieux, Karine +3 more·2015·Journal of Cerebral Blood Flow & Metabolism

Abstract

Although growth factors and anti-apoptotic peptides have been shown to be neuroprotective in stroke models, translation of these experimental findings to clinic is hampered by limited penetration of peptides to the brain. Here, we show that a large peptide like the basic fibroblast growth factor (bFGF) and a small peptide inhibitor of caspase-3 (z-DEVD-FMK) can effectively be transported to the brain after systemic administration by incorporating these peptides to brain-targeted nanoparticles (NPs). Chitosan NPs were loaded with peptides and then functionalized by conjugating with antibodies directed against the transferrin receptor-1 on brain endothelia to induce receptor-mediated transcytosis across the blood—brain barrier (BBB). Pre-ischemic systemic administration of bFGF- or z-DEVD-FMK-loaded NPs significantly decreased the infarct volume after 2-hour middle cerebral artery occlusion and 22-hour reperfusion in mice. Co-administration of bFGF- or z-DEVD-FMK-loaded NPs reduced the infarct volume further and provided a 3-hour therapeutic window. bFGF-loaded NPs were histologically detected in the brain parenchyma and also restored ischemia-induced Akt dephosphorylation. The neuroprotection was not observed when receptor-mediated transcytosis was inhibited with imatinib or when bFGF-loaded NPs were not conjugated with the targeting antibody, which enables them to cross the BBB. Nanoparticles targeted to brain are promising drug carriers to transport large as well as small BBB-impermeable therapeutics for neuroprotection against stroke.

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Crossref · 10.1038/jcbfm.2014.220

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  • To cross tissue barriers, nanoparticles are either negatively charged on the surface, or capable of binding to receptors on the cell surface, or densely packed around a metal core.

    “To cross the tissue barriers, nanoparticles are either negatively charged on the surface (519), or capable of binding to receptors on the cell surface (670), or densely packed around a metal core (291).”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [670]

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Authors
Yemisci, M., Caban, S., Gursoy-Ozdemir, Y., Lule, S., Novoa-Carballal, R., Riguera, R., Fernandez-Megia, E., Andrieux, K., Couvreur, P., Capan, Y., & Dalkara, T.
Affiliations
  • Department of Neurology, Faculty of Medicine, Institute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara, Turkey
  • Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey
  • Department of Organic Chemistry and Center for Research in Biological Chemistry and Molecular Materials (CIQUS), University of Santiago de Compostela, Santiago de Compostela, Spain
  • Universidade de Santiago de Compostela (ES)
  • Université Paris-Sud (FR)
  • Institut Galien Paris-Sud UMR CNRS 8612, Faculty of Pharmacy, University of Paris-Sud XI, Chátenay-Malabry, France
  • Hacettepe University (TR)
Corresponding author
Dalkara, Turgay
Venue
Journal of Cerebral Blood Flow & Metabolism
Published
2015-03
Volume
35
Issue
3
Pages
469-475
ISSN
  • 0271-678X (ISSN-L)
  • 1559-7016
OpenAlex
W1971415580
Cited by
118
References
30
Citations by year
2026: 4 · 2025: 3 · 2024: 13 · 2023: 5 · 2022: 15 · 2021: 12 · 2020: 10 · 2019: 16 · 2018: 11 · 2017: 12 · 2016: 11 · 2015: 6
FWCI
3.67
Type
journal article
Language
en
Open access
Locations
  • Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion)
  • HAL (submittedVersion)
  • Hispana (submittedVersion)
  • Repositorio institucional da Universidade de Santiago de Compostela (University of Santiago de Compostela) (submittedVersion)
  • Hacettepe University Institutional Repository (hacettepe.edu.tr) (submittedVersion, other-oa)
Funders
  • Türkiye Bilimsel ve Teknolojik Araştırma Kurumu (109S017)
  • Türkiye Bilimler Akademisi
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
Keywords
blood-brain barrier, peptide delivery, neuroprotection, stroke, chitosan nanoparticles, transferrin receptor 1, receptor-mediated transcytosis, basic fibroblast growth factor, Z-DEVD-FMK, caspase-3 inhibition, middle cerebral artery occlusion, infarct size, Akt dephosphorylation, imatinib, therapeutic window
MeSH terms
Animals, Blood-Brain Barrier, Male, Oligopeptides, Fibroblast Growth Factor 2, Neuroprotective Agents, Stroke, Mice, Nanoconjugates

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