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<p>Hypochlorous acid (HClO), as a crucial reactive oxygen species, plays significant roles in both physiological and pathological processes, particularly in the progression of neuroinflammation and neurodegenerative diseases. In this study, a novel near-infrared ratiometric fluorescent probe, Indole-NI-HClO, was designed and synthesized based on a naphthalimide-indole fused chromophore. Featuring a methyl thioether group as the specific recognition site, the probe operates through oxidation-induced modulation of intramolecular charge transfer mechanism for sensitive HClO detection. Spectroscopic characterization demonstrated excellent sensing performance, including a low detection limit (0.32 µM), a large Stokes shift, rapid response kinetics (within 30&#xa0;s), and high selectivity. Cellular experiments confirmed good biocompatibility, with the probe exhibiting low cytotoxicity in SH-SY5Y neuroblastoma cells where cell viability remained above 93% after 24&#xa0;h of incubation, and successful ratiometric imaging of both exogenous and endogenous HClO. Furthermore, the probe enabled visualization of endogenously produced HClO in zebrafish models under inflammatory stimulation. This work establishes Indole-NI-HClO as an effective molecular tool for investigating HClO-related biological functions and disease mechanisms in complex biological systems.</p>

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A Ratiometric Fluorescent Probe Based on Naphthalimide - Indole Scaffold for Imaging Hypochlorous Acid in Neuroin- Flammatory Models

  • 期刊论文

  • 发表日期：

    2026年4月9日

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  • Meijie Zhu,
  • Mengru Zhou,
  • Zhiwei Liu,
  • Zhiju Li,
  • Xiaodong Wang,
  • Min Zhang

摘要

Hypochlorous acid (HClO), as a crucial reactive oxygen species, plays significant roles in both physiological and pathological processes, particularly in the progression of neuroinflammation and neurodegenerative diseases. In this study, a novel near-infrared ratiometric fluorescent probe, Indole-NI-HClO, was designed and synthesized based on a naphthalimide-indole fused chromophore. Featuring a methyl thioether group as the specific recognition site, the probe operates through oxidation-induced modulation of intramolecular charge transfer mechanism for sensitive HClO detection. Spectroscopic characterization demonstrated excellent sensing performance, including a low detection limit (0.32 µM), a large Stokes shift, rapid response kinetics (within 30 s), and high selectivity. Cellular experiments confirmed good biocompatibility, with the probe exhibiting low cytotoxicity in SH-SY5Y neuroblastoma cells where cell viability remained above 93% after 24 h of incubation, and successful ratiometric imaging of both exogenous and endogenous HClO. Furthermore, the probe enabled visualization of endogenously produced HClO in zebrafish models under inflammatory stimulation. This work establishes Indole-NI-HClO as an effective molecular tool for investigating HClO-related biological functions and disease mechanisms in complex biological systems.