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  • Title: Identification of a peptide ligand recognizing dysfunctional endothelial cells for targeting atherosclerosis.
    Author: Thapa N, Hong HY, Sangeetha P, Kim IS, Yoo J, Rhee K, Oh GT, Kwon IC, Lee BH.
    Journal: J Control Release; 2008 Oct 06; 131(1):27-33. PubMed ID: 18680772.
    Abstract:
    Targeting ligands to dysfunctional or activated endothelial cells overlying atherosclerotic plaques could provide tools for selective drug delivery to atherosclerotic lesions. To identify peptides selectively targeting dysfunctional endothelial cells, a phage library was screened against tumor necrosis factor-alpha (TNF-alpha) activated bovine aortic endothelial cells (BAECs). Five rounds of biopanning were carried out and the phage clones selected were examined for their DNA inserts. A phage clone displaying the CLWTVGGGC sequence occurred most frequently and was found to bind specifically to TNF-alpha activated BAECs over untreated cells. On the other hand, bindings of the phage clone to human umbilical vein endothelial cells, lymphatic endothelial cells, and epithelial cells were minimal. Flow cytometric and fluorescence microscopic studies showed the preferential binding of the CLWTVGGGC peptide to TNF-alpha activated BAECs compared to untreated cells. In vivo studies demonstrated selective homing and co-localization of the CLWTVGGGC peptide to dysfunctional endothelial cells overlying atherosclerotic plaques in low-density lipoprotein receptor-deficient mice. These results demonstrate that the CLWTVGGGC peptide could specifically recognize dysfunctional endothelial cells at atherosclerotic plaques and be used as a targeting ligand for drug delivery and imaging of atherosclerosis.
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