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Photodynamic therapy (PDT) is a non-invasive cancer treatment modality that entails the administration of photosensitizers and light irradiation. Previously, we have established a polycation-containing hematoporphyrin (aHP) formulation, demonstrating superior anti-tumor efficacy compared to original hematoporphyrin (HP) in vivo. To reveal the variance in anti-tumor efficacy between them, we conducted timelapse imaging of rat gastric mucosa cell-line (RGM1) and its cancerous derivative (RGK45) treated with the porphyrins, and also analyzed their cellular localization and glycan chain expression on cellular membranes. Timelapse imaging of RGK45 treated with aHP revealed swelling, rupturing of cells, and subsequent scattering of small vesicles upon light irradiation, contrasting with the unchanged morphology of RGK45 treated with HP throughout the same irradiation duration. Furthermore, aHP exhibited a more concentrated cellular localization on cell membranes compared to HP with more diffuse fluorescence within cells. Additionally, neither aHP nor HP induced swelling or rupturing of cellular membranes in RGM1. Flow cytometry analysis demonstrated significantly higher fluorescence of wheat germ agglutinin conjugated dye in RGK45 compared to RGM1 (* p < 0.05), suggesting differential glycan expression patterns. These findings collectively suggest that the cellular toxicity of aHP may be augmented in RGK45 due to its heightened affinity towards negatively charged structures on cellular membranes and its preferential localization on them. The observed membrane rupturing and release of vesicles may confer an abscopal effect in addition to its direct PDT effect, thereby positioning aHP as a promising next-generation photosensitizer.

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• Creative Commons BY-NC-ND Attribution-NonCommercial-NoDerivs 4.0 International
  

  This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License.
  https://creativecommons.org/licenses/by-nc-nd/4.0/

Keyword: photodynamic therapy, hematoporphyrin, polycation, cell adhesive, cellular membrane, glycan

Date published: 2024-08-23

Publisher: The Society for Free Radical Research Japan

Journal:

• Journal of Clinical Biochemistry and Nutrition (ISSN: 09120009) vol. 75 issue. 3 p. 197-203 24-88

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Manuscript type: Publisher's version (Version of record)

MDR DOI:

First published URL: https://doi.org/10.3164/jcbn.24-88

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Updated at: 2024-11-25 16:30:47 +0900

Published on MDR: 2024-11-25 16:30:47 +0900