A pH-Gated Fluorescent Probe for Visualizing Hypochlorous Acid: From Pyroptosis to Tumor Imaging

Area of Science:

• Chemical Biology
• Biomedical Imaging
• Fluorescent Probes

Background:

• In vivo visualization of hypochlorous acid (HOCl) is hindered by tissue autofluorescence and non-specific activation.
• pH is a critical indicator of physiological and pathological states, offering a cue for disease detection.
• Advanced molecular tools integrating near-infrared (NIR) emission and signal gating are needed to overcome current visualization limitations.

Purpose of the Study:

• To develop a pH-gated, dual-locked, near-infrared (NIR) fluorescent probe for selective detection of hypochlorous acid (HOCl) in vivo.
• To address limitations of autofluorescence and nonspecific activation in current HOCl visualization methods.
• To provide a tool for enhanced disease diagnosis through accurate HOCl detection.

Main Methods:

• Construction of a pH-gated dual-locked NIR fluorescent probe (Ac-HEP) using an acridine scaffold and pH-responsive piperazine moieties.
• Utilizing a dual-locked fluorescence-activation strategy for selective HOCl detection.
• Validation of Ac-HEP in pyroptosis and inflammation zebrafish models, and tumor diagnosis in live mice.

Main Results:

• Ac-HEP demonstrated immediate fluorescence activation in acidic environments, enhancing HOCl recognition specificity.
• The probe successfully imaged a pyroptosis model and monitored HOCl in real-time during zebrafish inflammation.
• High-contrast tumor diagnosis was achieved in live mice, showcasing its utility for oxidative stress analysis.

Conclusions:

• The developed pH-gated, dual-locked fluorescent probe (Ac-HEP) offers a new strategy for HOCl detection in various pathological conditions.
• Ac-HEP provides a robust tool for spatiotemporal analysis of oxidative stress.
• This probe represents a significant advancement for disease diagnosis using fluorescent imaging.