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

Our plain-English summary of Water-Soluble Truncated Fatty Acid-Porphyrin Conjugates Provide Photo-Sensitizer Activity for Photodynamic Therapy in Malignant Mesothelioma, by S. Bonsall, S. Hubbard, U. Jithin, et al (Cancers, 2022).

The study

• Authors: S. Bonsall, S. Hubbard, U. Jithin, J. Anslow, D. Todd, C. Rowding, T. Filarowski, G. Duly, R. Wilson, J. Porter, S. Turega, S. Haywood-Small
• Journal: Cancers
• Published: 2022;14(21)
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This laboratory study from Sheffield Hallam University, UK, tested three newly made light-activated drugs (photosensitizers), C5SHU, C6SHU and C7SHU, for photodynamic therapy of malignant mesothelioma. No patients were involved and asbestos exposure was not studied. The drugs were applied to two human mesothelioma cell lines (biphasic MSTO-211H and epithelioid NCI-H28) and a non-cancerous mesothelial cell line (Met-5a), which were then exposed to light. All three drugs collected outside the cell nucleus. Viability was measured as a percentage of untreated cells. With C5SHU at 5 µg/mL, 48 hours after light, it was 22% versus 100% without light in MSTO-211H cells, and 16% versus 116% in NCI-H28 cells. C5SHU at that dose with light also reduced viability of the non-cancerous Met-5a cells (about 11% at 48 hours). It harmed MSTO-211H cells without light at higher doses. The authors concluded that C5SHU was the most effective of the three. They noted that further confirmation is needed. They also noted that activity in non-cancerous cells suggests the drugs also accumulate in healthy tissue, and that MSTO-211H results varied most between experiments.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) study: chemical synthesis of three porphyrin photosensitizers and testing of their light-activated (photodynamic) effect on cultured cell lines
• Who was studied: Commercial cell lines: human mesothelioma lines MSTO-211H (biphasic) and NCI-H28 (epithelioid), and the non-cancerous human mesothelial line MET-5a (Met-5a). No patients.
• Exposure: Not an asbestos exposure study. Cells were treated with the photosensitizers C5SHU, C6SHU or C7SHU at 5, 10, 15 and 20 µg/mL. They were then either irradiated for 15 minutes on a 15 W light box or kept in the dark.
• Main results:
  • All three photosensitizers showed similar uptake and localization in all three cell lines, outside the nucleus.
  • In water, C5SHU showed the least evidence of stacking (aggregation) of the three compounds.
  • In the WST-8 assay, cell viability was expressed as a percentage of untreated cells.
  • MSTO-211H cells, C5SHU 5 µg/mL, 48 hours: 22% viability with light vs 100% in the dark (WST-8 assay, relative to untreated cells).
  • NCI-H28 cells, C5SHU 5 µg/mL, 48 hours: 16% viability with light vs 116% in the dark (WST-8 assay, relative to untreated cells).
  • Non-cancerous Met-5a cells, C5SHU 5 µg/mL with light (WST-8 assay, relative to untreated cells): viability about 28% at 24 hours and about 11% at 48 hours.
  • C5SHU at 48 hours, concentration giving a 50% reduction in viable cells (EC50): 2.8 plus or minus 1.5 µg/mL in MSTO-211H, 6 plus or minus 1 µg/mL in NCI-H28, and 5.1 plus or minus 1 µg/mL in Met-5a.
  • Flow cytometry, C5SHU at 10 µg/mL with light: NCI-H28 cells died mainly by necrosis (16% apoptotic, 53% necrotic). MSTO-211H cells died mainly by apoptosis (49% apoptotic, 34% necrotic).
  • Without light, NCI-H28 cells treated with C5SHU stayed about 95% viable at all doses. MSTO-211H cells showed significant dark toxicity at 48 hours: 63.6% viable at 15 µg/mL and 46.1% viable at 20 µg/mL.
  • In Met-5a cells at 48 hours after C5SHU with light, viable cells decreased significantly at all doses, mainly by necrosis.
• The authors' conclusion: The authors concluded that C5SHU, the compound with the shortest chain length and lowest hydrophobic surface area, was the most effective photosensitizer and targeted MSTO-211H cells most effectively. They put it forward as a candidate for further development.
• Limitations the authors state:
  • The MSTO-211H findings for C5SHU need further confirmation, because viability was low in vehicle controls and dark toxicity was substantial at the higher doses.
  • Activity of C5SHU in the non-cancerous Met-5a cells suggests the photosensitizers also accumulate in healthy tissue.
  • The biphasic MSTO-211H cell line gave the most variable results between experiments.
  • The light source was not standardized; the authors suggested an LED system with a defined wavelength and fluence rate.
  • The study did not examine possible effects on blood vessels or the immune system.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Clinical Trial, Biphasic Mesothelioma, Epithelioid, Mesothelial Cells, Apoptosis, Necrosis.

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