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

Authors
Ryu, Ju HeeShin, Jung-YounKim, Sun AhKang, Sun-WoongKim, HyunjoonKang, SeokyungChoi, KuiwonKwon, Ick ChanKim, Byung-SooKim, Kwangmeyung
Issue Date
9월-2013
Publisher
ELSEVIER SCI LTD
Keywords
Matrix metalloproteinase; Albumin; Molecular imaging; Angiogenesis; Fluorescence
Citation
BIOMATERIALS, v.34, no.28, pp.6871 - 6881
Indexed
SCIE
SCOPUS
Journal Title
BIOMATERIALS
Volume
34
Number
28
Start Page
6871
End Page
6881
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/102302
DOI
10.1016/j.biomaterials.2013.05.074
ISSN
0142-9612
Abstract
Matrix metalloproteinase (MMP)-2 and MMP-9 have been known to play the role of essential mediators in angiogenesis. Non-invasive in vivo 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 36 nm 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. (C) 2013 Elsevier Ltd. All rights reserved.
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