Locally Administered Photodynamic Therapy for Cancer Using Nano-Adhesive Photosensitizer
Photodynamic therapy (PDT) is a great potential anti-tumor therapy owing to its non-invasiveness and high spatiotemporal selectivity. However, systemically administered photosensitizers diffuse in the skin and the eyes for a long duration, which cause phototoxicity to bright light and sunlight. Ther...
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MDPI AG
2023-08-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/8/2076 |
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| author | Yoshiki Komatsu Toru Yoshitomi Van Thi Hong Doan Hiromi Kurokawa Saori Fujiwara Naoki Kawazoe Guoping Chen Hirofumi Matsui |
| author_facet | Yoshiki Komatsu Toru Yoshitomi Van Thi Hong Doan Hiromi Kurokawa Saori Fujiwara Naoki Kawazoe Guoping Chen Hirofumi Matsui |
| author_sort | Yoshiki Komatsu |
| collection | DOAJ |
| description | Photodynamic therapy (PDT) is a great potential anti-tumor therapy owing to its non-invasiveness and high spatiotemporal selectivity. However, systemically administered photosensitizers diffuse in the skin and the eyes for a long duration, which cause phototoxicity to bright light and sunlight. Therefore, following PDT, patients must avoid exposure of to light and sunlight to avoid this phototoxicity. In this study, we have developed a locally administered PDT using nano-adhesive porphyrin with polycations consisting of quaternary ammonium salt groups (aHP) as a photosensitizer. The aHP, approximately 3.0 nm in diameter, adhered the negatively charged cell membrane via electrostatic interaction. The aHP localized to the endosome via cell adhesion and induced apoptosis upon 635 nm light irradiation. On being administered subcutaneously on the tumor, 30% of the injected aHP remained in the administered sites. However, low-molecular-weight hematoporphyrin dihydrochloride (HP) disappeared due to rapid diffusion. PDT with locally administered aHP showed a higher anti-tumor effect after light irradiation at 635 nm for three days compared to low-molecular-weight HP. Intraperitoneal administration of HP caused severe phototoxicity upon irradiation with ultraviolet A at 10 J cm<sup>−2</sup>, whereas aHP did not cause phototoxicity because its diffusion into the skin could be suppressed, probably due to the high-molecular weight of aHP. Therefore, locally administered PDT with aHP is a potential PDT having high therapeutic efficacy without phototoxicity. |
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| id | doaj.art-8d3545d300184e369eef24d72b3e0264 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T23:39:42Z |
| publishDate | 2023-08-01 |
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| series | Pharmaceutics |
| spelling | doaj.art-8d3545d300184e369eef24d72b3e02642023-11-19T02:36:24ZengMDPI AGPharmaceutics1999-49232023-08-01158207610.3390/pharmaceutics15082076Locally Administered Photodynamic Therapy for Cancer Using Nano-Adhesive PhotosensitizerYoshiki Komatsu0Toru Yoshitomi1Van Thi Hong Doan2Hiromi Kurokawa3Saori Fujiwara4Naoki Kawazoe5Guoping Chen6Hirofumi Matsui7Research Center for Macromolecules and Biomaterials, National Institute for Materials Science, 1-1 Namiki, Tsukuba 305-0044, Ibaraki, JapanResearch Center for Macromolecules and Biomaterials, National Institute for Materials Science, 1-1 Namiki, Tsukuba 305-0044, Ibaraki, JapanResearch Center for Macromolecules and Biomaterials, National Institute for Materials Science, 1-1 Namiki, Tsukuba 305-0044, Ibaraki, JapanDivision of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Ibaraki, JapanResearch Center for Macromolecules and Biomaterials, National Institute for Materials Science, 1-1 Namiki, Tsukuba 305-0044, Ibaraki, JapanResearch Center for Macromolecules and Biomaterials, National Institute for Materials Science, 1-1 Namiki, Tsukuba 305-0044, Ibaraki, JapanResearch Center for Macromolecules and Biomaterials, National Institute for Materials Science, 1-1 Namiki, Tsukuba 305-0044, Ibaraki, JapanDivision of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Ibaraki, JapanPhotodynamic therapy (PDT) is a great potential anti-tumor therapy owing to its non-invasiveness and high spatiotemporal selectivity. However, systemically administered photosensitizers diffuse in the skin and the eyes for a long duration, which cause phototoxicity to bright light and sunlight. Therefore, following PDT, patients must avoid exposure of to light and sunlight to avoid this phototoxicity. In this study, we have developed a locally administered PDT using nano-adhesive porphyrin with polycations consisting of quaternary ammonium salt groups (aHP) as a photosensitizer. The aHP, approximately 3.0 nm in diameter, adhered the negatively charged cell membrane via electrostatic interaction. The aHP localized to the endosome via cell adhesion and induced apoptosis upon 635 nm light irradiation. On being administered subcutaneously on the tumor, 30% of the injected aHP remained in the administered sites. However, low-molecular-weight hematoporphyrin dihydrochloride (HP) disappeared due to rapid diffusion. PDT with locally administered aHP showed a higher anti-tumor effect after light irradiation at 635 nm for three days compared to low-molecular-weight HP. Intraperitoneal administration of HP caused severe phototoxicity upon irradiation with ultraviolet A at 10 J cm<sup>−2</sup>, whereas aHP did not cause phototoxicity because its diffusion into the skin could be suppressed, probably due to the high-molecular weight of aHP. Therefore, locally administered PDT with aHP is a potential PDT having high therapeutic efficacy without phototoxicity.https://www.mdpi.com/1999-4923/15/8/2076polycationporphyrintissue adhesivecell adhesivephotodynamic therapyphototoxicity |
| spellingShingle | Yoshiki Komatsu Toru Yoshitomi Van Thi Hong Doan Hiromi Kurokawa Saori Fujiwara Naoki Kawazoe Guoping Chen Hirofumi Matsui Locally Administered Photodynamic Therapy for Cancer Using Nano-Adhesive Photosensitizer Pharmaceutics polycation porphyrin tissue adhesive cell adhesive photodynamic therapy phototoxicity |
| title | Locally Administered Photodynamic Therapy for Cancer Using Nano-Adhesive Photosensitizer |
| title_full | Locally Administered Photodynamic Therapy for Cancer Using Nano-Adhesive Photosensitizer |
| title_fullStr | Locally Administered Photodynamic Therapy for Cancer Using Nano-Adhesive Photosensitizer |
| title_full_unstemmed | Locally Administered Photodynamic Therapy for Cancer Using Nano-Adhesive Photosensitizer |
| title_short | Locally Administered Photodynamic Therapy for Cancer Using Nano-Adhesive Photosensitizer |
| title_sort | locally administered photodynamic therapy for cancer using nano adhesive photosensitizer |
| topic | polycation porphyrin tissue adhesive cell adhesive photodynamic therapy phototoxicity |
| url | https://www.mdpi.com/1999-4923/15/8/2076 |
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