γ-Glutamyl transpeptidase–activated indole-quinolinium based cyanine as a fluorescence turn-on nucleolus-targeting probe for cancer cell detection and inhibition

Huanxin Xue, Jiaye Lu, Hongwei Yan, Ju Huang, Hai Bin Luo, Man Shing Wong, Yuqi Gao*, Xiaolei Zhang*, Lei Guo*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

14 Citations (Scopus)

Abstract

A nucleolus as a prominent sub-nuclear, membraneless organelle plays a crucial role in ribosome biogenesis, which is in the major metabolic demand in a proliferating cell, especially in aggressive malignancies. We develop a γ-glutamyltranspeptidase (GGT)-activatable indole-quinolinium (QI) based cyanine consisting of a novel tripeptide fragment (Pro-Gly-Glu), namely QI-PG-Glu as a turn-on red fluorescent probe for the rapid detection of GGT-overexpressed A549 cancer cells in vivo. QI-PG-Glu can be triggered by GGT to rapidly release an activated fluorophore, namely HQI, in two steps including the cleavage of the γ-glutamyl group recognized by GGT and the rapid self-driven cyclization of the Pro-Gly linker. HQI exhibits dramatically red fluorescence upon binding to rRNA for imaging of nucleolus in live A549 cells. HQI also intervenes in rRNA biogenesis by declining the RNA Polymerase I transcription, thus resulting in cell apoptosis via a p53 dependent signaling pathway. Our findings may provide an alternative avenue to develop multifunctional cancer cell-specific nucleolus-targeting fluorescent probes with potential anti-cancer effects.

Original languageEnglish
Article number122898
JournalTalanta
Volume237
DOIs
Publication statusPublished - 15 Jan 2022

Scopus Subject Areas

  • Analytical Chemistry

User-Defined Keywords

  • Fluorescent probe
  • Nucleolus-targeting
  • p53
  • RNA Polymerase I
  • γ-Glutamyl transpeptidase

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