Non-invasive optical imaging of matrix metalloproteinase activity with albumin-based fluorogenic nanoprobes during angiogenesis in amouse hindlimb ischemia model

Ju Hee Ryu, Jung Youn Shin, Sun Ah Kim, Sun Woong Kang, Hyunjoon Kim, Seokyung Kang, Kuiwon Choi, Ick Chan Kwon, Byung Soo Kim, Kwangmeyung Kim

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Matrix metalloproteinase (MMP)-2 and MMP-9 have been known to play the role of essential mediators in angiogenesis. Non-invasive invivo imaging approach using imaging probes is a potential method of detecting MMP activity in living animals, wherein imaging probes must include the characteristics of non-toxicity, specific targetability, and reasonable signal intensity. Here, we developed MMP-specific and self-quenched human serum albumin (HSA)-based (MMP-HSA) nanoprobes for non-invasive optical imaging of MMP activity during angiogenesis in the mouse hindlimb ischemia model. MMP-specific fluorogenic peptide probes, which were self-quenched with a near-infrared fluorophore and a quencher, were covalently conjugated to HSA (MMP-HSA nanoprobes). MMP-HSA nanoprobes formed stable nanoparticle structures of approximately 36nm in diameter. Strongly self-quenched MMP-HSA nanoprobes boosted intense fluorescence signals in the presence of MMP-2 and MMP-9. Furthermore, MMP-HSA nanoprobes showed no cytotoxicity in cell culture. Importantly, intravenous injection of MMP-HSA nanoprobes provided longer blood half-life and successful non-invasive optical imaging of MMP activity during angiogenesis in the mouse hindlimb ischemia model. In addition, the MMP activity visualized by MMP-HSA nanoprobes was consistent with the results of zymography, Western blot, and immunohistochemistry. MMP-HSA nanoprobes may be useful for monitoring of the initial process of angiogenesis through non-invasive MMP imaging.

Original languageEnglish
Pages (from-to)6871-6881
Number of pages11
JournalBiomaterials
Volume34
Issue number28
DOIs
StatePublished - Sep 2013

Bibliographical note

Funding Information:
This work is supported by M.D.-Ph.D. Program ( 2010-0019863 , 2010-0019864 ), Ministry of Health and Welfare ( A120247 ), the National Research Foundation of Korea ( 2010-0020352 ), KIST Young Fellow Program , and the Intramural Research Programs (Theragnosis) of KIST .

Keywords

  • Albumin
  • Angiogenesis
  • Fluorescence
  • Matrix metalloproteinase
  • Molecular imaging

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