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Photodynamic Therapy with Blended Conducting Polymer/Fullerene Nanoparticle Photosensitizers
Published on: October 28, 2015
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.
Abstract:
Clinical trials evaluating intrapleural photodynamic therapy (PDT) are ongoing for mesothelioma. Several issues still hinder the development of PDT, such as those related to the inherent properties of photosensitizers. Herein, we report the synthesis, photophysical, and photobiological properties of three porphyrin-based photosensitizers conjugated to truncated fatty acids (C5SHU to C7SHU). Our photosensitizers exhibited excellent water solubility and high PDT efficiency in mesothelioma. As expected, absorption spectroscopy confirmed an increased aggregation as a consequence of extending the fatty acid chain length. In vitro PDT activity was studied using human mesothelioma cell lines (biphasic MSTO-211H cells and epithelioid NCI-H28 cells) alongside a non-malignant mesothelial cell line (MET-5A). The PDT effect of these photosensitizers was initially assessed using the colorimetric WST-8 cell viability assay and the mode of cell death was determined via flow cytometry of Annexin V-FITC/PI-stained cells. Photosensitizers appeared to selectively localize within the non-nuclear compartments of cells before exhibiting high phototoxicity. Both apoptosis and necrosis were induced at 24 and 48 h. As our pentanoic acid-derivatized porphyrin (C5SHU) induced the largest anti-tumor effect in this study, we put this forward as an anti-tumor drug candidate in PDT and photo-imaging diagnosis in mesothelioma.
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.

