2026-03-12T10:41:23Z https://kumadai.repo.nii.ac.jp/oai

oai:kumadai.repo.nii.ac.jp:02000816 2025-01-23T04:22:35Z 415:416

Novel cyclic peptides facilitating transcellular blood-brain barrier transport of macromolecules in vitro and in vivo Shunsuke, Yamaguchi Shingo, Ito Takeshi, Masuda Pierre-Olivier, Couraud Sumio, Ohtsuki Cyclic peptide Phage display technology Brain delivery Macromolecule Brain delivery of nanoparticles and macromolecular drugs depends on blood-brain barrier (BBB)-permeable carriers. In this study, we searched for cyclic heptapeptides facilitating BBB permeation of M13 phages by phage library screening using a transcellular permeability assay with hCMEC/D3 cell monolayers, a human BBB model. The M13 phage, which is larger than macromolecular drugs and nanoparticles, served as a model macromolecule. The screen identified cyclic heptapeptide SLSHSPQ (SLS) as a human BBB-permeable peptide. The SLS-displaying phage (SLS-phage) exhibited improved permeation across the cell monolayer of monkey and rat BBB co-culture models. The SLS-phage internalized into hCMEC/D3 cells via macropinocytosis and externalized via the exosome excretion pathway. SLS-phage distribution into brain parenchyma was observed in mice after intravenous administration. Moreover, liposome permeated across the BBB as cyclic SLS peptide conjugates. In conclusion, the cyclic SLS heptapeptide is a novel carrier candidate for brain delivery of macromolecular drugs and nanoparticles. journal article Elsevier 2020-05-10 AM application/pdf Journal of Controlled Release 321 744 755 0168-3659 https://kumadai.repo.nii.ac.jp/record/2000816/files/10.1016_j.jconrel.2020.03.001.pdf http://hdl.handle.net/2298/0002000816 https://kumadai.repo.nii.ac.jp/records/2000816 eng (C) 2020 Elsevier B.V. All rights reserved. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/ open access