Lysosomes Targeting pH Activable Imaging-Guided Photodynamic Agents.

Area of Science:

• Organic Chemistry
• Photochemistry
• Biomedical Engineering

Background:

• Photodynamic therapy (PDT) faces challenges with current photosensitizer (PS) clinical approval and selective tumor targeting.
• Reducing side effects requires photosensitizers that accumulate specifically in malignant cells.

Purpose of the Study:

• To develop novel lysosome-targeting, pH-responsive theranostic photosensitizers based on BODIPY derivatives.
• To evaluate their photophysical properties, in vitro cytotoxicity, and imaging potential for cancer therapy.

Main Methods:

• Synthesis of aniline- and iodine-substituted BODIPY derivatives (1-3).
• Spectroscopic, electrochemical, and computational analyses to characterize photophysical properties.
• In vitro cytotoxicity assays (IC50) and cellular uptake studies using fluorescence microscopy and co-localization with LysoTracker.

Main Results:

• Compounds 1-3 demonstrated quenched fluorescence and 1O2 emission, restored under acidic conditions (pH ~4-5) due to amine protonation.
• Established pKa values and pH-dependent emissive properties for the new PS.
• Confirmed lysosomal targeting and activation, significant light-induced cytotoxicity (IC50: 0.06–0.16 μM) against HeLa cells, and low dark toxicity for compounds 2 and 3.

Conclusions:

• The novel BODIPY derivatives function as effective lysosome-targeting, pH-responsive theranostic agents for photodynamic therapy.
• Their pH-dependent activation and potent cytotoxicity offer a promising strategy to overcome limitations of existing PDT photosensitizers.