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Article Dans Une Revue Journal of Cerebral Blood Flow and Metabolism Année : 2015

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

Muge Yemisci
  • Fonction : Auteur
Secil Caban
  • Fonction : Auteur
Yasemin Gursoy-Ozdemir
  • Fonction : Auteur
Sevda Lule
  • Fonction : Auteur
Ramon Novoa-Carballal
  • Fonction : Auteur
Ricardo Riguera
  • Fonction : Auteur
Eduardo Fernandez-Megia
  • Fonction : Auteur
Karine Andrieux
Yilmaz Capan
  • Fonction : Auteur
Turgay Dalkara
  • Fonction : Auteur

Résumé

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.

Dates et versions

hal-04119814 , version 1 (06-06-2023)

Identifiants

Citer

Muge Yemisci, Secil Caban, Yasemin Gursoy-Ozdemir, Sevda Lule, Ramon Novoa-Carballal, et al.. Systemically Administered Brain-Targeted Nanoparticles Transport Peptides across the Blood—Brain Barrier and Provide Neuroprotection. Journal of Cerebral Blood Flow and Metabolism, 2015, 35 (3), pp.469-475. ⟨10.1038/jcbfm.2014.220⟩. ⟨hal-04119814⟩
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