Open AccessOptical imaging of MMP-12 active form in inflammation and aneurysm
Author(s) -
Mahmoud Razavian,
Thomas Bordenave,
Dimitris Georgiadis,
Fabrice Beau,
Jiasheng Zhang,
Reza Golestani,
Jakub Toczek,
Jaejoon Jung,
Yunpeng Ye,
Hye-Yeong Kim,
Joungho Han,
Vincent Dive,
Laurent Devel,
Mehran M. Sadeghi
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep38345
Subject(s) - matrix metalloproteinase , immunostaining , fluorophore , aneurysm , in vivo , inflammation , chemistry , drug delivery , pathology , medicine , fluorescence , biophysics , biology , biochemistry , immunology , radiology , immunohistochemistry , physics , microbiology and biotechnology , organic chemistry , quantum mechanics
Matrix metalloproteinase (MMP)-12 plays a key role in the development of aneurysm. Like other members of MMP family, MMP-12 is produced as a proenzyme, mainly by macrophages, and undergoes proteolytic activation to generate an active form. Accordingly, molecular imaging of the MMP-12 active form can inform of the pathogenic process in aneurysm. Here, we developed a novel family of fluorescent probes based on a selective MMP-12 inhibitor, RXP470.1 to target the active form of MMP-12. These probes were stable in complex media and retained the high affinity and selectivity of RXP470.1 for MMP-12. Amongst these, probe 3 containing a zwitterionic fluorophore, ZW800-1, combined a favorable affinity profile toward MMP-12 and faster blood clearance. In vivo binding of probe 3 was observed in murine models of sterile inflammation and carotid aneurysm. Binding specificity was demonstrated using a non-binding homolog. Co-immunostaining localized MMP-12 probe binding to MMP-12 positive areas and F4/80 positive macrophages in aneurysm. In conclusion, the active form of MMP-12 can be detected by optical imaging using RXP470.1-based probes. This is a valuable adjunct for pathophysiology research, drug development, and potentially clinical applications.