An ONOO^-/Viscosity-Sensitive and Mitochondria-Targeted Near-Infrared Fluorophore for Real-Time Tracking Mitophagy and...

Area of Science:

• Biomedical Engineering
• Chemical Biology
• Oncology

Background:

• Malignant tumors represent a significant global health challenge.
• Dual-functional agents offer promise for simultaneous cancer diagnosis and therapy.
• Organelle-targeted photodynamic therapy (PDT) enhances treatment efficacy.

Purpose of the Study:

• To develop a mitochondria- and endoplasmic reticulum (ER)-targeted fluorescent probe, HCy-BA.
• To evaluate HCy-BA for near-infrared (NIR) fluorescence imaging of reactive oxygen species and viscosity.
• To assess the photodynamic therapy efficacy and real-time monitoring capabilities of HCy-BA.

Main Methods:

• Synthesis of the hemicyanine-based probe HCy-BA incorporating phenylboronic acid and α-β unsaturated ester.
• Evaluation of NIR fluorescence imaging for reactive oxygen species (e.g., ONOO-) and viscosity in cancer cells.
• Assessment of singlet oxygen (1O2) generation and phototoxicity in vitro.
• In vivo studies using tumor-bearing mice to evaluate tumor suppression and treatment monitoring.

Main Results:

• HCy-BA demonstrated high sensitivity and specificity for NIR fluorescence imaging of ONOO- and viscosity, distinguishing cancer from normal cells.
• The probe exhibited potent 1O2 generation and significant phototoxicity against tumor cells.
• Effective tumor suppression was observed in vivo.
• HCy-BA enabled real-time monitoring of mitochondrial autophagy during PDT, visualizing treatment progression.

Conclusions:

• HCy-BA is a promising dual-functional agent for integrated cancer diagnosis and therapy.
• The probe's ability to target specific organelles and monitor treatment offers new avenues for precision oncology.
• This work provides insights into designing advanced molecular tools for combined diagnostic and therapeutic applications.