Peroxynitrite Responsive Second Near-Infrared Cyanine Dye J‑Aggregate for Drug-Induced Hepatotoxicity Monitoring

Area of Science:

• Biomedical Engineering
• Chemical Biology
• Medical Imaging

Background:

• Drug-induced hepatotoxicity is a significant clinical challenge.
• Peroxynitrite (ONOO^-) is an early biomarker for drug-induced liver injury.
• Existing in vivo imaging methods for ONOO^- are limited by autofluorescence and light scattering.

Purpose of the Study:

• To develop a novel probe for sensitive and real-time detection of ONOO^- in vivo.
• To overcome the limitations of visible and NIR-I window probes for hepatotoxicity monitoring.

Main Methods:

• Synthesized a peroxynitrite (ONOO^-) responsive cyanine dye, IR-1061 J-aggregate (J_IR-1061), with absorption in the NIR-IIb window (1580 nm).
• Conjugated J_IR-1061 with rare earth nanoparticles (RENPs) emitting at 1550 nm to create a dual-mode probe (RENPs-J_IR-1061).
• Evaluated the probe's response to ONOO^- and its efficacy for real-time hepatotoxicity monitoring in vivo.

Main Results:

• The developed probe, RENPs-J_IR-1061, exhibits a significant red shift (>500 nm) and operates in the NIR-IIb region.
• The probe demonstrated a fast and sensitive response to ONOO^-, indicated by activatable NIR-IIb fluorescence and photoacoustic signal changes.
• Successfully applied for real-time in vivo monitoring of drug-induced hepatotoxicity.

Conclusions:

• RENPs-J_IR-1061 is a promising dual-mode imaging probe for detecting ONOO^-.
• This probe facilitates real-time, unambiguous visualization of drug-induced hepatotoxicity in vivo.
• Offers a potential new tool for early diagnosis and management of liver injury.