In situ localization of alkaline phosphatase activity in tumor cells by an aggregation-induced emission fluorophore-based probes

Bioorg Med Chem. 2020 Feb 15;28(4):115284. doi: 10.1016/j.bmc.2019.115284. Epub 2019 Dec 19.

Abstract

In situ detection of certain specific enzyme activities in cells is deeply attached to tumor diagnosis. Conventional enzyme-responsive fluorescent probes have difficulty detecting targeted enzymes in situ in cells due to the low detection accuracy caused by the spread of fluorescence probes. In order to solve this problem, we have designed and synthesized an enzyme-responsive, water-soluble fluorescent probe with AIE characteristics, which could aggregate and precipitate to produce in situ fluorescence when reacting with the targeted enzyme in cells. The AIE fluorophore (TPEQH) was utilized to design the enzyme-responsive, fluorescent probe (TPEQHA) by introducing a phosphate group on to it, which could be specifically decomposed by the targeted enzyme, namely alkaline phosphatase (ALP). In tumor cells, TPEQH was highly produced due to the interaction of phosphate on the TPEQHA and the overexpressed ALP. Water-insoluble TPEQH then precipitated and release fluorescence in situ, thereby successfully detecting the ALP. Furthermore, the expression level of ALP could be determined by the fluorescence intensity of TPEQH with higher accuracy due to the inhibition of TPEQH leak, which demonstrated a potential application of in suit ALP detection in both clinical diagnosis and scientific research of tumor.

Keywords: AIE probe; ALP; Tumor fluorescence imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / analysis*
  • Alkaline Phosphatase / metabolism
  • Cell Line
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Fluorescent Dyes / chemical synthesis
  • Fluorescent Dyes / chemistry*
  • Fluorescent Dyes / pharmacology
  • HeLa Cells
  • Humans
  • Molecular Structure
  • Optical Imaging
  • Protein Aggregates
  • Spectrometry, Fluorescence
  • Structure-Activity Relationship

Substances

  • Fluorescent Dyes
  • Protein Aggregates
  • Alkaline Phosphatase