Water-Soluble Truncated Fatty Acid-Porphyrin Conjugates Provide Photo-Sensitizer Activity for Photodynamic Therapy in

Sam Bonsall1, Simeon Hubbard1, Uthaman Jithin1

  • 1Biomolecular Sciences Research Centre, Sheffield Hallam University, City Campus, Howard Street, Sheffield S1 1WB, UK.

Cancers
|November 11, 2022
PubMed

Insights

New porphyrin-based photosensitizers show promise for photodynamic therapy (PDT) in mesothelioma treatment. The C5SHU compound demonstrated significant anti-tumor effects and potential for photo-imaging diagnosis.

Area of Science:

  • * Medicinal Chemistry
  • * Photobiology
  • * Oncology

Background:

  • * Photodynamic therapy (PDT) is under investigation for mesothelioma treatment.
  • * Limitations in photosensitizer properties hinder PDT development.
  • * Porphyrin-based compounds offer potential as photosensitizers.

Purpose of the Study:

  • * To synthesize and characterize novel porphyrin-based photosensitizers conjugated to fatty acids (C5SHU to C7SHU).
  • * To evaluate their photophysical, photobiological, and anti-tumor properties for mesothelioma.
  • * To assess their potential for PDT and photo-imaging diagnosis.

Main Methods:

  • * Synthesis and characterization of three porphyrin-based photosensitizers.
  • * Absorption spectroscopy to assess aggregation.
  • * In vitro studies using mesothelioma cell lines (MSTO-211H, NCI-H28) and a non-malignant cell line (MET-5A).
  • * WST-8 cell viability assay and flow cytometry (Annexin V-FITC/PI staining) to determine cell death modes.

Main Results:

  • * Photosensitizers exhibited good water solubility and high PDT efficiency.
  • * Increasing fatty acid chain length led to increased aggregation.
  • * Photosensitizers localized in non-nuclear cellular compartments, showing high phototoxicity.
  • * Both apoptosis and necrosis were induced in cancer cells.
  • * C5SHU demonstrated the most significant anti-tumor effect.

Conclusions:

  • * Porphyrin-based photosensitizers, particularly C5SHU, are effective in PDT for mesothelioma.
  • * C5SHU shows potential as an anti-tumor drug candidate and for photo-imaging diagnosis.
  • * Further development of these photosensitizers could advance mesothelioma treatment options.

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