In vivo optical imaging of membrane-type matrix metalloproteinase (MT-MMP) activity

Lei Zhu, Fan Zhang, Ying Ma, Gang Liu, Kwangmeyung Kim, Xuexun Fang, Seulki Lee, Xiaoyuan Chen

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Herein we demonstrate for the first time that a fluorogenic probe can be used as an in vivo imaging agent for visualizing activities of membrane-tethered, membrane-type matrix metalloproteinases (MT-MMPs). An MT-MMP fluorogenic probe that consisted of an MT1-MMP (MMP-14) substrate and near-infrared (NIR) dye-quencher pair exhibited rapid, efficient boosts in fluorescence upon cleavage by MT1-MMP in tumor-bearing mice. In particular, unlike similar fluorogenic probes designed to target extracellular, soluble-type MMPs (EC-MMPs)-which can be cleared from the bloodstream after activation-the fluorescence signals activated by MT1-MMP enable clear visualization of MT1-MMP-positive tumors in animal models for up to 24 h. The results indicate that a simple form of a fluorogenic probe that is less effective in EC-MMP imaging is an effective probe for imaging MT-MMP activities in vivo. These findings can be widely applied to designing probes and to applications targeting various membrane-anchored proteases in vivo.

Original languageEnglish
Pages (from-to)2331-2338
Number of pages8
JournalMolecular Pharmaceutics
Volume8
Issue number6
DOIs
Publication statusPublished - 2011 Dec 5
Externally publishedYes

Keywords

  • activatable probe
  • fluorogenic probe
  • membrane-type matrix metalloproteinase
  • optical imaging
  • protease

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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