Identification of a peptide ligand recognizing dysfunctional endothelial cells for targeting atherosclerosis

Narendra Thapa, Hai Yan Hong, Purushotham Sangeetha, In-San Kim, Jeongsoo Yoo, Kyehan Rhee, Goo Taeg Oh, Ick Chan Kwon, Byung Heon Lee

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)27-33
Number of pages7
JournalJournal of Controlled Release
Volume131
Issue number1
DOIs
Publication statusPublished - 2008 Oct 6
Externally publishedYes

Fingerprint

Atherosclerosis
Endothelial Cells
Ligands
Peptides
Bacteriophages
Atherosclerotic Plaques
Clone Cells
Tumor Necrosis Factor-alpha
LDL Receptors
Human Umbilical Vein Endothelial Cells
Drug Delivery Systems
Fluorescence
Epithelial Cells
DNA
Pharmaceutical Preparations

Keywords

  • Atherosclerosis
  • Dysfunctional endothelial cells
  • Peptide
  • Phage display
  • Tumor necrosis factor-alpha

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Identification of a peptide ligand recognizing dysfunctional endothelial cells for targeting atherosclerosis. / Thapa, Narendra; Hong, Hai Yan; Sangeetha, Purushotham; Kim, In-San; Yoo, Jeongsoo; Rhee, Kyehan; Oh, Goo Taeg; Kwon, Ick Chan; Lee, Byung Heon.

In: Journal of Controlled Release, Vol. 131, No. 1, 06.10.2008, p. 27-33.

Research output: Contribution to journalArticle

Thapa, Narendra ; Hong, Hai Yan ; Sangeetha, Purushotham ; Kim, In-San ; Yoo, Jeongsoo ; Rhee, Kyehan ; Oh, Goo Taeg ; Kwon, Ick Chan ; Lee, Byung Heon. / Identification of a peptide ligand recognizing dysfunctional endothelial cells for targeting atherosclerosis. In: Journal of Controlled Release. 2008 ; Vol. 131, No. 1. pp. 27-33.
@article{fb93d4ca374c40539f9eaa50305aaebc,
title = "Identification of a peptide ligand recognizing dysfunctional endothelial cells for targeting atherosclerosis",
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.",
keywords = "Atherosclerosis, Dysfunctional endothelial cells, Peptide, Phage display, Tumor necrosis factor-alpha",
author = "Narendra Thapa and Hong, {Hai Yan} and Purushotham Sangeetha and In-San Kim and Jeongsoo Yoo and Kyehan Rhee and Oh, {Goo Taeg} and Kwon, {Ick Chan} and Lee, {Byung Heon}",
year = "2008",
month = "10",
day = "6",
doi = "10.1016/j.jconrel.2008.07.013",
language = "English",
volume = "131",
pages = "27--33",
journal = "Journal of Controlled Release",
issn = "0168-3659",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Identification of a peptide ligand recognizing dysfunctional endothelial cells for targeting atherosclerosis

AU - Thapa, Narendra

AU - Hong, Hai Yan

AU - Sangeetha, Purushotham

AU - Kim, In-San

AU - Yoo, Jeongsoo

AU - Rhee, Kyehan

AU - Oh, Goo Taeg

AU - Kwon, Ick Chan

AU - Lee, Byung Heon

PY - 2008/10/6

Y1 - 2008/10/6

N2 - 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.

AB - 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.

KW - Atherosclerosis

KW - Dysfunctional endothelial cells

KW - Peptide

KW - Phage display

KW - Tumor necrosis factor-alpha

UR - http://www.scopus.com/inward/record.url?scp=52049123528&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=52049123528&partnerID=8YFLogxK

U2 - 10.1016/j.jconrel.2008.07.013

DO - 10.1016/j.jconrel.2008.07.013

M3 - Article

C2 - 18680772

AN - SCOPUS:52049123528

VL - 131

SP - 27

EP - 33

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

IS - 1

ER -