ZFIN ID: ZDB-PUB-180302-5
An activatable near-infrared fluorescent probe for dipeptidyl peptidase IV and its bioimaging applications in living cells and animals
Liu, T., Ning, J., Wang, B., Dong, B., Li, S., Tian, X., Yu, Z., Peng, Y., Wang, C., Zhao, X., Huo, X., Sun, C.P., Cui, J.N., Feng, L., Ma, X.
Date: 2018
Source: Analytical chemistry   90(6): 3965-3973 (Journal)
Registered Authors: Wang, Bo
Keywords: none
MeSH Terms:
  • Animals
  • Dipeptidyl Peptidase 4/analysis*
  • Dipeptidyl Peptidase 4/blood
  • Dipeptidyl Peptidase 4/metabolism
  • Enzyme Assays/methods
  • Fluorescent Dyes/chemistry*
  • Hep G2 Cells
  • Humans
  • Infrared Rays
  • Mice
  • Microscopy, Confocal/methods
  • Neoplasms/diagnostic imaging
  • Neoplasms/enzymology
  • Optical Imaging/methods*
  • Zebrafish
PubMed: 29493228 Full text @ Anal. Chem.
ABSTRACT
Visualization of endogenous disease-associated enzymes is of great clinical significance, as it could allow earlier clinical diagnosis and timely intervention. Herein, we first synthesized and characterized an enzyme-activatable near-infrared fluorescent probe, GP-DM, for determining the activity of dipeptidyl peptidase IV (DPP IV), which is associated with various pathological processes, especially in diabetes and malignant tumors. GP-DM emitted significant turn-on NIR fluorescent signals simultaneously in response to DPP IV, making it favorable for accurately and dynamically monitoring DPP IV activity in vitro and in vivo. GP-DM exhibited excellent specificity and sensitivity in DPP IV imaging, as indicated by its higher catalytic activity than other human serine hydrolases and by its strong anti-interference ability to a complex biological matrix, which was fully characterized in a series of phenotyping reactions and inhibition assays. Encouraged by the advantages mentioned above, we successfully used GP-DM to evaluate endogenous DPP IV activity in various biological samples (plasma and tissue preparations) and living tumor cells, and performed real-time in vivo bioimaging of DPP IV in zebrafish and tumor-bearing nude mice. All of the results reflected and highlighted the potential application value of GP-DM in the early detection of pathologies, individual tailoring of drug therapy, and image-guided tumor resection. Furthermore, our results revealed that DPP IV, a key target enzyme, is closely associated with the migration and proliferation of cancer cells, and regulating the biological activity of DPP IV may be a useful approach for cancer therapy.
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