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Molecular targeting of atherosclerotic plaques by a stabilin-2-specific peptide ligand
- Molecular targeting of atherosclerotic plaques by a stabilin-2-specific peptide ligand
- Lee G.Y.; Kim J.-H.; Oh G.T.; Lee B.-H.; Kwon I.C.; Kim I.-S.
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- Journal of Controlled Release
- vol. 155, no. 2, pp. 211 - 217
- SCI; SCIE; SCOPUS
- Many cells, including macrophages, accumulate in atherosclerotic lesions, destabilizing plaques and driving plaque disruption. Therefore, macrophages serve as useful targets for atherosclerosis treatment and imaging. Stabilin-2 is a transmembrane protein expressed predominantly in macrophages and endothelial cells. In the present study, we found that stabilin-2 was widely expressed in atherosclerotic plaques than in normal vessel walls, and was present not only in macrophages but also in endothelial and smooth muscle cells in plaques. We used phage display technology to identify peptides that specifically bound to stabilin-2. After four rounds of selection, the most commonly isolated peptide had the sequence CRTLTVRKC, and was named S2P. We confirmed that this peptide specifically bound to stabilin-2-expressing cells in vitro and sinus endothelial cells in the spleen and lymph nodes in vivo. A FITC-conjugated synthetic CRTLTVRKC peptide was shown to home to atherosclerotic plaques in Ldlr-/- mice and to co-localize with endothelial cells, macrophages, and smooth muscle cells in such plaques. S2P conjugated to hydrophobically modified glycol chitosan nanoparticles was efficiently delivered to atherosclerotic plaques. These results show that the CRLTLTVRKC peptide homes to plaques by targeting stabilin-2; the peptide shows promise as a drug delivery moiety for, and an aid to molecular imaging of, atherosclerosis and other inflammatory diseases. © 2011 Elsevier B.V.
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