Halogen-modified photosensitizers: Inducing mitochondrial dysfunction for tumor suppression

Area of Science:

• Materials Science
• Nanotechnology
• Biomedical Engineering

Background:

• Optimizing halogenated organic photosensitizers (PSs) for cancer therapy is challenging.
• Direct comparison of fluorine (F) vs. bromine (Br) terminal halogens in PSs is needed.
• Nanoformulation of PSs can improve therapeutic delivery and efficacy.

Purpose of the Study:

• To construct and compare two PSs, LYD-F and LYD-Br, with identical skeletons but different terminal halogens.
• To evaluate their photophysical properties, photothermal performance, and anti-tumor efficacy.
• To determine if fluorine incorporation optimizes PS performance for cancer treatment.

Main Methods:

• Synthesized LYD-F and LYD-Br photosensitizers.
• Nano-formulated PSs using DSPE-PEG2000 into LYD-F NPs and LYD-Br NPs.
• Characterized molar extinction coefficients, photothermal conversion efficiency (PCE), and reactive oxygen species (ROS) generation under 808 nm laser irradiation.
• Evaluated anti-tumor effects, including tumor ablation and immune response, in vivo.

Main Results:

• LYD-F exhibited a higher molar extinction coefficient than LYD-Br.
• LYD-F NPs showed superior photothermal performance (ΔT = 43.83°C, PCE = 62.39%) compared to LYD-Br NPs (ΔT = 38.76°C, PCE = 55.02%).
• LYD-F NPs generated significantly higher ROS levels than LYD-Br NPs.
• LYD-F NPs treatment resulted in effective tumor ablation, mitochondrial damage, and triggered an anti-tumor immune response, suppressing lung metastasis.

Conclusions:

• Fluorinated photosensitizers (LYD-F) demonstrate enhanced photophysical properties and therapeutic efficacy over brominated counterparts (LYD-Br).
• Nanoformulation of LYD-F NPs provides superior photothermal and ROS-generating capabilities for cancer therapy.
• Introducing fluorine atoms into PSs is an effective strategy for optimizing tumor therapeutic performance and inducing anti-tumor immunity.