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Halogen-modified photosensitizers: Inducing mitochondrial dysfunction for tumor suppression.

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Fluorine-containing photosensitizers (PSs) offer superior tumor therapy performance compared to bromine-containing ones. LYD-F nanoparticles demonstrated enhanced photothermal effects, reactive oxygen species generation, and potent anti-tumor activity, including immune response induction.

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HalogensPhotodynamic therapyPhotosensitizersPhotothermal therapyTumor

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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.