Detection of apoptosis in a rat model of focal cerebral ischemia using a homing peptide selected from in vivo phage display

Hai Yan Hong, Jung Sook Choi, Yoon Jung Kim, Hwa Young Lee, Wonjung Kwak, Jeongsoo Yoo, Jae Tae Lee, Tae Hwan Kwon, In-San Kim, Hyung Soo Han, Byung Heon Lee

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Focal cerebral ischemia, known as stroke, is caused by a sudden interruption in the blood supply to the brain. We attempted to identify peptides that can home to ischemic stroke tissue and detect the apoptosis of cells. A phage library displaying random peptides was screened for homing peptides to ischemic stroke tissue in a rat transient middle cerebral artery (MCA) occlusion model. After three rounds of in vivo screening, a phage clone displaying the most frequently occurring CLEVSRKNC sequence was selected. The CLEVSRKNC-phage preferentially homed to ischemic stroke tissue after intravenous administration into the MCA occlusion rats. The fluorescein-labeled synthetic CLEVSRKNC peptide, but not a scrambled control peptide, homed to ischemic stroke tissue with a lack of homing to non-ischemic brain tissue. The CLEVSRKNC peptide co-localized with a portion of neuronal cells, rather than with astrocytes, undergoing apoptosis at the penumbra region of stroke lesions. In autoradiographic studies, the uptake of the 131 I-labeled CLEVSRKNC peptide into an ischemic lesion increased at the first day and peaked at the third day after the injury. These results demonstrate that the CLEVSRKNC peptide can home to ischemic stroke tissue, while detecting apoptotic neuronal cells, and suggest it has applications as a targeting moiety for molecular imaging and selective drug delivery to stroke tissue.

Original languageEnglish
Pages (from-to)167-172
Number of pages6
JournalJournal of Controlled Release
Volume131
Issue number3
DOIs
Publication statusPublished - 2008 Nov 12
Externally publishedYes

Fingerprint

Brain Ischemia
Bacteriophages
Stroke
Apoptosis
Peptides
Middle Cerebral Artery Infarction
Peptide Library
Molecular Imaging
Brain
Fluorescein
Astrocytes
Intravenous Administration
Clone Cells
Wounds and Injuries
Pharmaceutical Preparations

Keywords

  • Apoptosis
  • Homing peptide
  • Imaging
  • Phage display
  • Stroke

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Detection of apoptosis in a rat model of focal cerebral ischemia using a homing peptide selected from in vivo phage display. / Hong, Hai Yan; Choi, Jung Sook; Kim, Yoon Jung; Lee, Hwa Young; Kwak, Wonjung; Yoo, Jeongsoo; Lee, Jae Tae; Kwon, Tae Hwan; Kim, In-San; Han, Hyung Soo; Lee, Byung Heon.

In: Journal of Controlled Release, Vol. 131, No. 3, 12.11.2008, p. 167-172.

Research output: Contribution to journalArticle

Hong, Hai Yan ; Choi, Jung Sook ; Kim, Yoon Jung ; Lee, Hwa Young ; Kwak, Wonjung ; Yoo, Jeongsoo ; Lee, Jae Tae ; Kwon, Tae Hwan ; Kim, In-San ; Han, Hyung Soo ; Lee, Byung Heon. / Detection of apoptosis in a rat model of focal cerebral ischemia using a homing peptide selected from in vivo phage display. In: Journal of Controlled Release. 2008 ; Vol. 131, No. 3. pp. 167-172.
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AB - Focal cerebral ischemia, known as stroke, is caused by a sudden interruption in the blood supply to the brain. We attempted to identify peptides that can home to ischemic stroke tissue and detect the apoptosis of cells. A phage library displaying random peptides was screened for homing peptides to ischemic stroke tissue in a rat transient middle cerebral artery (MCA) occlusion model. After three rounds of in vivo screening, a phage clone displaying the most frequently occurring CLEVSRKNC sequence was selected. The CLEVSRKNC-phage preferentially homed to ischemic stroke tissue after intravenous administration into the MCA occlusion rats. The fluorescein-labeled synthetic CLEVSRKNC peptide, but not a scrambled control peptide, homed to ischemic stroke tissue with a lack of homing to non-ischemic brain tissue. The CLEVSRKNC peptide co-localized with a portion of neuronal cells, rather than with astrocytes, undergoing apoptosis at the penumbra region of stroke lesions. In autoradiographic studies, the uptake of the 131 I-labeled CLEVSRKNC peptide into an ischemic lesion increased at the first day and peaked at the third day after the injury. These results demonstrate that the CLEVSRKNC peptide can home to ischemic stroke tissue, while detecting apoptotic neuronal cells, and suggest it has applications as a targeting moiety for molecular imaging and selective drug delivery to stroke tissue.

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