In vivo imaging of β-galactosidase stimulated activity in hepatocellular carcinoma using ligand-targeted fluorescent probe

Abstract Development of targeted, selective, and noninvasive fluorescent probes for in vivo visualization of tumor-associated overexpressed enzymes are highly anticipated for cancer diagnosis and therapy. Herein, we developed a noninvasive fluorescent probe ( DCDHF- β gal ) for the sensitive detecti...

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Bibliographic Details
Published in:Biomaterials 2017-04, Vol.122, p.83-90
Main Authors: Kim, Eun-Joong, Kumar, Rajesh, Sharma, Amit, Yoon, Byungkwon, Kim, Hyun Min, Lee, Hyunseung, Hong, Kwan Soo, Kim, Jong Seung
Format: Article
Language:English
Subjects:
Advanced Basic Science
Animals
beta-Galactosidase - metabolism
Biomarkers, Tumor - metabolism
Carcinoma, Hepatocellular - metabolism
Carcinoma, Hepatocellular - pathology
Dentistry
Enzyme Activation
Fluorescent Dyes - chemistry
Fluorescent probe
Galactose - chemistry
Galactose - pharmacokinetics
Hep G2 Cells
Hepatocellular
Humans
In vivo imaging
Ligands
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Microscopy, Fluorescence - methods
Molecular Imaging - methods
Molecular Probe Techniques
Ratiometric
Reproducibility of Results
Sensitivity and Specificity
β-galactosidase
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Summary:Abstract Development of targeted, selective, and noninvasive fluorescent probes for in vivo visualization of tumor-associated overexpressed enzymes are highly anticipated for cancer diagnosis and therapy. Herein, we developed a noninvasive fluorescent probe ( DCDHF- β gal ) for the sensitive detection, and in vivo visualization of β-galactosidase in hepatocyte HepG2 cells and its xenograft model. As a model system for in vivo targeted imaging, DCDHF- β gal possessing galactose unit selectively target hepatocyte and monitor the β-galactosidase activity with deep tissue penetration, and low background interference. DCDHF- β gal was activated by intracellular β-galactosidases as the driving force for the release of NIR fluorophore, thereby exhibiting ratiometric optical response. Initial fluorescence emission measured at 615 nm was changed to fluorescence at 665 nm upon activation of DCDHF- β gal with β-galactosidase. Ratiometric fluorescence detection of β-galactosidase was also observed in hepatocellular carcinoma cells and tumor xenograft. The noninvasive in vivo optical imaging facilitated by targeted and enzyme-activated imaging agent would be useful in various biomedical and diagnostic applications.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2017.01.009