Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 134, Issue 33, Pages 13730-13737Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ja303931b
Keywords
-
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan [22000006, 20689001, 19890047, 21659024, 24659042]
- SENTAN, JST
- Tokyo Biochemical Research Foundation
- Inoue Foundation for Science
- Takeda Science Foundation
- Research Foundation for Pharmaceutical Sciences
- Konica Minolta Science and Technology Foundation
- The Asahi Glass Foundation
- Astellas Foundation for Research on Metabolic Disorders
- Grants-in-Aid for Scientific Research [22000006, 24655147, 20689001, 21659024, 24659042, 19890047] Funding Source: KAKEN
Ask authors/readers for more resources
Near-infrared (NIR) fluorescence probes are especially useful for simple and noninvasive in vivo imaging inside the body because of low autofluorescence and high tissue transparency in the NIR region compared with other wavelength regions. However, existing NIR fluorescence probes for matrix metalloproteinases (MMPs), which are tumor, atherosclerosis, and inflammation markers, have various disadvantages, especially as regards sensitivity. Here, we report a novel design strategy to obtain a NIR fluorescence probe that is rapidly internalized by free diffusion and well retained intracellularly after activation by extracellular MMPs. We designed and synthesized four candidate probes, each consisting of a cell permeable or nonpermeable NIR fluorescent dye as a Forster resonance energy transfer (FRET) donor linked to the NIR dark quencher BHQ-3 as a FRET acceptor via a MMP substrate peptide. We applied these probes for detection of the MMP activity of cultured HT-1080 cells, which express MMP2 and MT1-MMP, by fluorescence microscopy. Among them, the probe incorporating BODIPY650/665, BODIPY-MIMP, clearly visualized the MMP activity as an increment of fluorescence inside the cells. We then applied this probe to a mouse xenograft tumor model prepared with HT-1080 cells. Following intratumoral injection of the probe, MMP activity could be visualized for much longer with BODIPY-MMP than with the probe containing SulfoCy5, which is cell impermeable and consequently readily washed out of the tissue. This simple design strategy should be applicable to develop a range of sensitive, rapidly responsive NIR fluorescence probes not only for MMP activity, but also for other proteases.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available