Molecular targeting of atherosclerotic plaques by a stabilin-2-specific peptide ligand
- Molecular targeting of atherosclerotic plaques by a stabilin-2-specific peptide ligand
- 이가영; 김종호; 오구택; 이병헌; 권익찬; 김인산
- Atherosclerosis; Targeting; Stabilin-2; Phage display; Nanoparticles
- Issue Date
- Journal of controlled release
- VOL 155, NO 2, 211-217
- 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.
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