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
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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.

Item Type: Article
Uncontrolled Keywords: apoptosis; mesothelioma; necrosis; photodynamic therapy; 1112 Oncology and Carcinogenesis
Identification Number: https://doi.org/10.3390/cancers14215446
SWORD Depositor: Symplectic Elements
Depositing User: Symplectic Elements
Date Deposited: 25 Nov 2022 17:34
Last Modified: 12 Oct 2023 09:01
URI: https://shura.shu.ac.uk/id/eprint/31071

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