A Near-Infrared Fluorescent Probe Based on Naphthalimide for Lysosomal Hydrogen m n;

Area of Science:

• Biochemistry
• Chemical Biology
• Molecular Imaging

Background:

• Hydrogen polysulfides (H₂Sₙ) are critical oxidized derivatives of hydrogen sulfide (H₂S) involved in physiological and pathological processes.
• Dysregulation of H₂Sₙ homeostasis is linked to various health disorders.
• A need exists for fluorescent probes capable of localizing lysosomes and detecting H₂Sₙ.

Purpose of the Study:

• To fabricate a novel near-infrared fluorescent probe for the specific detection of lysosomal H₂Sₙ.
• To evaluate the probe's performance in terms of sensitivity, specificity, and response time.
• To demonstrate the probe's utility in biological systems, including cell imaging and in vivo studies.

Main Methods:

• Synthesis of a near-infrared fluorophore by conjugating 1,8-naphthalimide with dicyanoisophorone (DCI).
• Incorporation of 2-fluoro-5-nitrobenzoate as the H₂Sₙ sensing unit and morpholine for lysosomal targeting.
• Characterization of the probe's fluorescence properties, sensing mechanism (ICT process), linear detection range, and detection limit.

Main Results:

• The probe exhibited minimal fluorescence in the absence of H₂Sₙ, with activation of the intramolecular charge transfer (ICT) process leading to fluorescence emission at 690 nm upon H₂Sₙ introduction.
• A linear detection range of 0.4–10 µM and a low detection limit of 15 nM for H₂Sₙ were achieved.
• The probe demonstrated excellent specificity, sensitivity, rapid response, a large Stokes shift, and negligible cytotoxicity.

Conclusions:

• A highly effective near-infrared fluorescent probe for lysosomal H₂Sₙ detection has been developed.
• The probe successfully detected endogenous and exogenous H₂Sₙ in A549 cell lysosomes and in zebrafish.
• This tool holds promise for advancing research into the biological roles of H₂Sₙ in health and disease.