RT Journal Article
T1 Systemically Administered Brain-Targeted Nanoparticles Transport Peptides across the Blood—Brain Barrier and Provide Neuroprotection
A1 Yemisci, Muge
A1 Caban, Secil
A1 Gursoy-Ozdemir, Yasemin
A1 Lule, Sevda
A1 Novoa Carballal, Ramón
A1 Riguera Vega, Ricardo
A1 Fernández Megía, Eduardo
A1 Andrieux, Karine
A1 Couvreur, Partick
A1 Capan, Yilmaz
A1 Dalkara, Turgay
K1 Cerebrovascular disease/stroke
K1 Caspases
K1 Growth factors/cytokines
K1 Nanoparticles
K1 Neuroprotection
AB 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
PB SAGE Publications
SN 0271-678X
YR 2015
FD 2015-03-01
LK http://hdl.handle.net/10347/16962
UL http://hdl.handle.net/10347/16962
LA eng
NO Yemisci, M., Caban, S., Gursoy-Ozdemir, Y., Lule, S., Novoa-Carballal, R., & Riguera, R. et al. (2015). Systemically Administered Brain-Targeted Nanoparticles Transport Peptides across the Blood—Brain Barrier and Provide Neuroprotection. Journal Of Cerebral Blood Flow & Metabolism, 35, 3, 469-475. doi: 10.1038/jcbfm.2014.220
NO Turgay Dalkara’s work is supported by the Turkish Academy of Sciences. This study is supported by The Scientific and Technological Research Council ofTurkey (TUBITAK, Project Number: 109S017)
DS Minerva
RD 23 abr 2026