A spiropyran with low pKa for tracking DNA G-quadruplexes and revealing the dissipation of ΔΨm with senescence using an in-situ switching strategy

Xinrong Tian, Jin Li, Yanhui Zhang, Ying Gao, Muhammad Wasim Afzal, Aoli Wang, Tony D. James, Yinjuan Bai, Yuan Guo

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Abstract

The in-situ fluorescence triggering of bioprobes only using endogenous bioforces is an ideal non-destructive real-time detection method, which is of particular interest to improve the accuracy of clinical diagnosis and treatment. We have recently reported a strategy of spiropyran in-situ switching triggered by endogenous biological forces in vivo to develop optical probes for this purpose. However, such probes, as with all spiropyrans, are sensitive to lysosomal acidity. We here present a spiropyran-based fluorescent probe TANG with low pKa, which can recognize intranuclear DNA G4s in situ without the aid of exogenous light or chemicals and is as stable to lysosomal acidity due to a decreased pKa value (4.3). Interestingly, despite the stability to lysosomal pH environment, the TANG spiropyran can be opened in situ by the negative membrane potential of extranuclear mitochondria (ΔΨm), causing a ratiometric change in fluorescence signals and providing the in-situ and real-time tracking of ΔΨm. Of note, ratiometric imaging using TANG indicates that ΔΨm decreases gradually with cellular senescence, which is to the best of our knowledge the first visualization of such mitochondrion-related aging processes using a ratiometric imaging approach.

Original languageEnglish
Article number131618
JournalSensors and Actuators B: Chemical
Volume359
Early online date23 Feb 2022
DOIs
Publication statusPublished - 15 May 2022

Bibliographical note

Funding Information:
We gratefully appreciate the financial support from NSF of China (21977082 and 22037002), the Natural Science Basic Research Plan in Shaanxi Province of China (2020JC-38), the Technology Plan Project of Xi'an of China (2019218214GXRC018CG019-GXYD18.1). GIST-48B cell lines were kindly provided by the group of Professor Jonathan A. Fletcher at Brigham and Women's Hospital in Boston. Tony D. James wishes to thank the Royal Society for a Wolfson Research Merit Award.

Funding Information:
We gratefully appreciate the financial support from NSF of China ( 21977082 and 22037002 ), the Natural Science Basic Research Plan in Shaanxi Province of China ( 2020JC-38 ), the Technology Plan Project of Xi'an of China ( 2019218214GXRC018CG019-GXYD18.1 ). GIST-48B cell lines were kindly provided by the group of Professor Jonathan A. Fletcher at Brigham and Women’s Hospital in Boston. Tony D. James wishes to thank the Royal Society for a Wolfson Research Merit Award.

Funding

We gratefully appreciate the financial support from NSF of China (21977082 and 22037002), the Natural Science Basic Research Plan in Shaanxi Province of China (2020JC-38), the Technology Plan Project of Xi'an of China (2019218214GXRC018CG019-GXYD18.1). GIST-48B cell lines were kindly provided by the group of Professor Jonathan A. Fletcher at Brigham and Women's Hospital in Boston. Tony D. James wishes to thank the Royal Society for a Wolfson Research Merit Award. We gratefully appreciate the financial support from NSF of China ( 21977082 and 22037002 ), the Natural Science Basic Research Plan in Shaanxi Province of China ( 2020JC-38 ), the Technology Plan Project of Xi'an of China ( 2019218214GXRC018CG019-GXYD18.1 ). GIST-48B cell lines were kindly provided by the group of Professor Jonathan A. Fletcher at Brigham and Women’s Hospital in Boston. Tony D. James wishes to thank the Royal Society for a Wolfson Research Merit Award.

Keywords

  • Fluorescent probes
  • G-quadruplexes
  • Membrane potential of mitochondria
  • Senescence
  • Senescent cells

ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • Instrumentation
  • Condensed Matter Physics
  • Surfaces, Coatings and Films
  • Metals and Alloys
  • Electrical and Electronic Engineering
  • Materials Chemistry

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