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A novel NIR fluorescent probe to image HNO during ferroptosis
Changyi Li1, Xiaokai Wang1, Xiaofei Zhu2
1Green Catalysis Center, College of Chemistry, Zhengzhou University, Zhengzhou, 450001, China.
Analytica Chimica Acta
|November 3, 2024
Summary
This study introduces a new near-infrared fluorescent probe (X-1) for detecting nitric oxide (HNO) signaling molecules during ferroptosis. The probe successfully visualized HNO in living cells and confirmed its role in cancer drug therapy.
Area of Science:
- Chemical Biology
- Molecular Imaging
- Biomedical Engineering
Background:
- Nitric oxide (HNO) is a critical reactive nitrogen species (RNS) and signaling molecule in physiological processes.
- Ferroptosis, a form of regulated cell death, involves significant production of RNS, yet HNO's role remains understudied, particularly in the near-infrared (NIR) spectrum.
- Developing advanced imaging tools is crucial for understanding HNO's involvement in cellular mechanisms like ferroptosis.
Purpose of the Study:
- To design and synthesize a novel NIR fluorescent probe (X-1) for selective HNO detection.
- To investigate the mechanism of HNO signaling during ferroptosis using the developed probe.
- To evaluate the probe's utility in live-cell imaging and its potential in cancer therapy research.
Main Methods:
- Synthesis of the NIR HNO fluorescent probe X-1 utilizing a tricyanofuran (TCF) derivative and a Staudinger linkage reaction.
- Characterization of probe X-1's selectivity, response time, detection limit, and biocompatibility using spectroscopic and cell-based assays.
- Application of probe X-1 for imaging exogenous and endogenous HNO in living cells and verifying its mechanism via high-resolution mass spectrometry (HRMS).
Main Results:
- A novel NIR fluorescent probe, X-1, was successfully synthesized for selective HNO detection at 660 nm emission.
- Probe X-1 demonstrated a rapid response (5 min), low detection limit, large Stokes shift (120 nm), and excellent anti-interference capabilities.
- The probe exhibited good biocompatibility and was effectively used for imaging HNO in living cells, revealing its role in ferroptosis.
Conclusions:
- HNO acts as a mediator of cellular signaling, with its concentration increasing during ferroptosis, particularly in the NIR range.
- The developed probe X-1 provides a valuable tool for studying HNO-related biological processes, including ferroptosis.
- The study confirmed that sorafenib, a cancer therapeutic, functions by inducing ferroptosis, a process visualized using the X-1 probe.
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