Engineering an activatable fluorescent probe for studying ONOO- in pyroptotic process

Jiankang Gong1, Xiaoyu Wang1, Hai-En Fan1

  • 1College of Health Science and Engineering, Hubei University, Wuhan, 430062, China.

Talanta
|September 18, 2023
PubMed

Insights

Researchers developed a new probe to detect peroxynitrite (ONOO-) during pyroptosis, a cell death process crucial for cancer treatment. This tool helps understand ONOO-’s role in pyroptosis and screen drugs that trigger it.

Area of Science:

  • Biomedical Science
  • Oncology
  • Cellular Biology

Background:

  • Pyroptosis is a programmed cell death pathway vital for cancer treatment, but its mechanisms remain largely unknown.
  • Reactive oxygen species (ROS), particularly peroxynitrite (ONOO-), are linked to pyroptosis and various diseases.
  • Understanding the ONOO- pyroptosis connection is crucial for advancing cancer therapies.

Purpose of the Study:

  • To investigate the role of ONOO- in pyroptosis during tumor treatment.
  • To develop a sensitive probe for detecting ONOO- fluctuations in real-time.
  • To explore the utility of this probe in evaluating chemotherapeutic drug efficacy.

Main Methods:

  • Fabrication of a novel near-infrared (NIR) probe, Rd700-PN, for ONOO- detection.
  • Utilizing Rd700-PN to monitor ONOO- levels during cellular pyroptosis.
  • Employing Rd700-PN to assess the pyroptosis-inducing capacity of anticancer drugs in vivo.

Main Results:

  • Rd700-PN successfully detected ONOO- fluctuations during cellular pyroptosis for the first time.
  • The probe demonstrated the ability to scout the pyroptosis induction by chemotherapeutic drugs in vivo.
  • This highlights a new method for studying the ONOO- and pyroptosis interplay.

Conclusions:

  • A novel NIR probe, Rd700-PN, was developed for sensitive and rapid ONOO- detection.
  • This study establishes a link between ONOO- and pyroptosis in cancer treatment.
  • Rd700-PN offers a valuable tool for elucidating pyroptosis mechanisms and screening novel antitumor drugs.