Water-soluble truncated fatty acid–porphyrin conjugates provide photo-sensitizer activity for photodynamic therapy in malignant mesothelioma

BONSALL, Sam, HUBBARD, Simeon, JITHIN, Uthaman, ANSLOW, Joseph, TODD, Dylan, ROWDING, Callum, FILAROWSKI, Tom, DULY, Greg, WILSON, Ryan, PORTER, Jack, TUREGA, Simon and HAYWOOD-SMALL, Sarah (2022). Water-soluble truncated fatty acid–porphyrin conjugates provide photo-sensitizer activity for photodynamic therapy in malignant mesothelioma. Cancers, 14 (21): 5446.

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Official URL: https://www.mdpi.com/2072-6694/14/21/5446
Open Access URL: https://www.mdpi.com/2072-6694/14/21/5446/pdf?vers... (Published version)
Link to published version:: https://doi.org/10.3390/cancers14215446


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.

Plain Text Summary

Malignant mesothelioma is a rare, fatal cancer with limited treatment options. Photodynamic therapy is an emerging treatment option which uses a drug (known as a photosensitizer) and a specific type of light to selectively destroy cancerous cells. We have synthesized new photosensitizing drugs by linking organic chemical structures (variable length fatty acid chains) to existing photosensitisers. These new photosensitizing drugs were characterized, and their cancer-killing capabilities were also assessed in malignant mesothelioma cells in the laboratory. We have found that one of the newly synthesized photosensitisers (C5SHU) appeared to cause a significant amount of cell death in the malignant mesothelioma cells in combination with light. C5SHU-induced cell death did not occur in the absence of light. Therefore, we propose that this photosensitizer—C5SHU—is a suitable anti-tumour drug candidate in this hard-to-treat cancer.

Item Type: Article
Additional Information: ** Article version: VoR ** From MDPI via Jisc Publications Router ** Licence for VoR version of this article: https://creativecommons.org/licenses/by/4.0/ ** Peer reviewed: TRUE **Journal IDs: eissn 2072-6694 **Article IDs: publisher-id: cancers-14-05446 **History: published_online 05-11-2022; collection 11-2022; accepted 28-10-2022; submitted 29-07-2022
Uncontrolled Keywords: Article, photodynamic therapy, mesothelioma, apoptosis, necrosis
Identification Number: https://doi.org/10.3390/cancers14215446
SWORD Depositor: Colin Knott
Depositing User: Colin Knott
Date Deposited: 07 Dec 2022 13:28
Last Modified: 12 Oct 2023 08:46
URI: https://shura.shu.ac.uk/id/eprint/31125

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