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Phonozen-mediated photodynamic therapy comparing two wavelengths in a mouse model of peritoneal carcinomatosis

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Abstract

Background

This study assessed the therapeutic efficacy of intraperitoneal photodynamic therapy (PDT) using photosensitizer activation at two different wavelengths, 405 and 664 nm, in a mouse model of peritoneal carcinomatosis.

Methods

The dark and light cytotoxicity of chlorin e6-polyvinylpyrrolidone (Phonozen) were measured in vitro under 402 ± 14 and 670 ± 18 nm LED activation in bioluminescent human gastric cancer cells, MKN45-luc. Cell viability was measured at 6 h after irradiation using the PrestoBlue assay. Corresponding in vivo studies were performed in athymic nude mice by intraperitoneal injection of 1 × 106 MKN45-luc cells. PDT was performed 10 d after tumor induction and comprised intraperitoneal injection of Phonozen followed by light irradiation at 3 h, delivered by a diffusing-tip optical fiber placed in the peritoneal cavity and coupled to a 405 or 664 nm diode laser to deliver a total energy of 50 J (20 mice per cohort). Whole-body bioluminescence imaging was used to track the tumor burden after PDT out to 130 days, and 5 mice in each cohort were sacrificed at 4 h post treatment to measure the acute tumor necrosis.

Results

Photosensitizer dose-dependent photocytotoxicity was higher in vitro at 405 than 664 nm. In vivo, PDT reduced the tumor growth rate at both wavelengths, with no statistically significant difference. There was substantial necrosis, and median survival was significantly prolonged at both wavelengths compared with controls (46 and 46 vs. 34 days).

Conclusions

Phonozen-mediated PDT results in significant cytotoxicity in vitro as well as tumor necrosis and prolonged survival in vivo following intraperitoneal light irradiation. Blue light was more photocytotoxic than red in vitro and had marginally higher efficacy in vivo.

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Data availability

The datasets used and analyzed during the current study available from the corresponding author on reasonable request.

Abbreviations

PC:

Peritoneal carcinomatosis

PDT:

Photodynamic therapy

PBS:

Phosphate-buffered saline

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Acknowledgements

We thank DongSung Biopharmaceuticals for generously providing Phonozen. This work was financially supported by a faculty research grant from Yonsei University College of Medicine, Seoul, S. Korea (6-2020-0088). Preliminary studies leading to this work were supported by the Terry Fox Research Institute.

Funding

The authors have no financial or non-financial interests directly or indirectly related to the work.

Author information

Authors and Affiliations

  1. Princess Margaret Cancer Research Tower, University Health Network, 15-314, 101 College Street, Toronto, ON, M5G 1L7, Canada

    Hyoung-Il Kim, Layla Pires & Brian C. Wilson

  2. Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea

    Hyoung-Il Kim

  3. Division of Upper Gastrointestinal Surgery, Gastric Cancer Center, Yonsei Cancer Center, Seoul, South Korea

    Hyoung-Il Kim

  4. Yonsei-Dongsung Photodynamic Therapy Research Center, Avison Biomedical Research Center, Yonsei University College of Medicine, Seoul, South Korea

    Hyoung-Il Kim, Sung-Ho Lee, Jong-Hyun Park, Jae Eun Yu, Sang Won Lee & Seung Hee Yang

  5. Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea

    Su-Jin Shin

  6. Department of Nano-Science and Technology, Graduate School of Convergence Science and Technology of Seoul National University, Seoul, South Korea

    Jong-Hyun Park

  7. Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada

    Brian C. Wilson

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  1. Hyoung-Il Kim
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Correspondence to Brian C. Wilson.

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Conflict of interest

This study was supported by a faculty research grant from Yonsei University College of Medicine, Seoul, S. Korea (6-2020-0088). Preliminary studies leading to this work were supported by the Terry Fox Research Institute. The funding sources were not involved in the study design, data collection or analysis, or manuscript preparation or submission.

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Kim, HI., Lee, SH., Shin, SJ. et al. Phonozen-mediated photodynamic therapy comparing two wavelengths in a mouse model of peritoneal carcinomatosis. Photochem Photobiol Sci 22, 2563–2572 (2023). https://doi.org/10.1007/s43630-023-00470-w

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