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Amino Acids

, Volume 48, Issue 7, pp 1641–1654 | Cite as

In vivo monitoring of angiogenesis in a mouse hindlimb ischemia model using fluorescent peptide-based probes

  • Subin Park
  • Jangwook Lee
  • Mi-hee Jo
  • Jin Hee Na
  • Sung-Gurl Park
  • Hyeon-Ki Jang
  • Sun-Woong Kang
  • Jong-Ho Kim
  • Byung-Soo Kim
  • Jae Hyung Park
  • Ick Chan Kwon
  • Ju Hee RyuEmail author
  • Kwangmeyung KimEmail author
Original Article

Abstract

Vascular endothelial growth factor receptor (VEGFR) and matrix metalloproteinase (MMP) are up-regulated in ischemic tissue and play pivotal roles in promoting angiogenesis. The purpose of the present study was to evaluate two fluorophore-conjugated peptide probes specific to VEGFR and MMP for dual-targeted in vivo monitoring of angiogenesis in a murine model of hindlimb ischemia. To this end, VEGFR-Probe and MMP-Probe were developed by conjugating distinct near-infrared fluorophores to VEGFR-binding and MMP substrate peptides, respectively. VEGFR-Probe exhibited specific binding to VEGFR on HUVECs, and self-quenched MMP-Probe produced strong fluorescence intensity in the presence of MMPs in vitro. Subsequently, VEGFR-Probe and MMP-Probe were successfully utilized for time course in vivo visualization of VEGFR or MMP, respectively. Simultaneous visualization provided information regarding the spatial distribution of these proteins, including areas of co-localization. This dual-targeted in vivo imaging approach will be useful for understanding the detailed mechanism of angiogenesis and for evaluating therapeutic angiogenesis.

Keywords

Vascular endothelial growth factor receptor Matrix metalloproteinase Molecular imaging Angiogenesis Fluorescence imaging 

Notes

Acknowledgments

This work was supported by Nano-Convergence Foundation (www.nanotech2020.org) funded by the Ministry of Science, ICT and Future Planning (MSIP, Korea) & the Ministry of Trade, Industry and Energy (MOTIE, KOREA) [project name: Development and Commercialization of Nanoparticle Sensor for Detecting Protease Activity], Development of High Medical Technology Project (HI14C2755) of KHIDI, and the Intramural Research Programs of KIST.

Compliance with ethical standards

Conflict of interest

There is no conflict of interest for any of the authors.

Supplementary material

726_2016_2225_MOESM1_ESM.docx (763 kb)
Electronic supplementary materials The online version of this article containing supplementary material, which is available to authorized users. This material includes synthetic scheme of the MMP peptide probe; in vitro cytotoxicity assay of the VEGFR-Probe and the MMP-Probe; and in vivo NIR fluorescence imaging of the probes without targeting peptide moieties. (DOCX 762 kb)

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Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  • Subin Park
    • 1
    • 2
  • Jangwook Lee
    • 1
  • Mi-hee Jo
    • 3
  • Jin Hee Na
    • 1
  • Sung-Gurl Park
    • 4
  • Hyeon-Ki Jang
    • 5
  • Sun-Woong Kang
    • 4
  • Jong-Ho Kim
    • 3
  • Byung-Soo Kim
    • 5
  • Jae Hyung Park
    • 2
  • Ick Chan Kwon
    • 1
    • 6
  • Ju Hee Ryu
    • 1
    Email author
  • Kwangmeyung Kim
    • 1
    Email author
  1. 1.Center for Theragnosis, Biomedical Research InstituteKorea Institute of Science and TechnologySeoulRepublic of Korea
  2. 2.Departments of Polymer Science and Chemical EngineeringSungkyunkwan UniversitySuwonRepublic of Korea
  3. 3.Department of Pharmaceutical Science, College of PharmacyKyung Hee UniversitySeoulRepublic of Korea
  4. 4.Next-generation Pharmaceutical Research CenterKorea Institute of ToxicologyDaejeonRepublic of Korea
  5. 5.School of Chemical and Biological EngineeringSeoul National UniversitySeoulRepublic of Korea
  6. 6.KU-KIST SchoolKorea UniversitySeoulRepublic of Korea

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