Development of a red-shifted photosensitizer for near-infrared photoimmunotherapy of cancer
Near-infrared photoimmunotherapy (NIR-PIT) is a recently described method for cancer treatment that utilizes an antibody-conjugated phthalocyanine photosensitizer and NIR light. In NIR-PIT, light of 690 nm wavelength is used to activate a photosensitizer, IR700, while longer-wavelength light penetra...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Journal of Photochemistry and Photobiology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666469024000058 |
| _version_ | 1827318555462336512 |
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| author | Yuto Goto Kanta Ando Hideo Takakura Kohei Nakajima Masato Kobayashi Osamu Inanami Tetsuya Taketsugu Mikako Ogawa |
| author_facet | Yuto Goto Kanta Ando Hideo Takakura Kohei Nakajima Masato Kobayashi Osamu Inanami Tetsuya Taketsugu Mikako Ogawa |
| author_sort | Yuto Goto |
| collection | DOAJ |
| description | Near-infrared photoimmunotherapy (NIR-PIT) is a recently described method for cancer treatment that utilizes an antibody-conjugated phthalocyanine photosensitizer and NIR light. In NIR-PIT, light of 690 nm wavelength is used to activate a photosensitizer, IR700, while longer-wavelength light penetrates deeper into tissues. Thus, more effective NIR-PIT would be achieved by using photosensitizers that are activated by longer-wavelength light. The absorption wavelength would be red-shifted by destabilizing the highest occupied molecular orbital (HOMO) energy level by introducing electron donating groups at the α positions of a phthalocyanine ring. In this study, we developed a red-shifted photosensitizer for NIR-PIT, KA800, whose absorption wavelength was red-shifted by the introduction of ethoxy groups to IR700. As intended, the absorption maximum of KA800 was red-shifted compared to IR700 by 84 nm. Although phototoxicity of the antibody-KA800 (Ab-KA800) conjugate was observed in cultured cancer cells, no therapeutic effect was observed in mice. This is because the cytotoxicity of Ab-KA800 was mainly due to singlet oxygen, which can be quenched by abundant antioxidants in vivo. KA800 had low reactivity with respect to axial ligand cleavage required for inducing cell death via aggregate formation, a unique cytotoxic mechanism in NIR-PIT. The axial ligand cleavage proceeds via the anion radical formation of the photosensitizer, and KA800 was found to be less likely to receive an electron than IR700. This may be due to the destabilization of the HOMO energy level of KA800. Therefore, our findings suggest that stabilizing the lowest unoccupied molecular orbital (LUMO) energy level would be better than destabilizing the HOMO energy level for developing a red-shifted photosensitizer for NIR-PIT. |
| first_indexed | 2024-03-08T02:01:07Z |
| format | Article |
| id | doaj.art-ae9cc01e20ad480b866e264cba63e411 |
| institution | Directory Open Access Journal |
| issn | 2666-4690 |
| language | English |
| last_indexed | 2024-04-25T00:04:00Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Photochemistry and Photobiology |
| spelling | doaj.art-ae9cc01e20ad480b866e264cba63e4112024-03-14T06:16:12ZengElsevierJournal of Photochemistry and Photobiology2666-46902024-04-0120100230Development of a red-shifted photosensitizer for near-infrared photoimmunotherapy of cancerYuto Goto0Kanta Ando1Hideo Takakura2Kohei Nakajima3Masato Kobayashi4Osamu Inanami5Tetsuya Taketsugu6Mikako Ogawa7Laboratory of Bioanalysis and Molecular Imaging, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, JapanLaboratory of Bioanalysis and Molecular Imaging, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, JapanLaboratory of Bioanalysis and Molecular Imaging, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, JapanLaboratory of Bioanalysis and Molecular Imaging, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, JapanDepartment of Chemistry, Faculty of Science, Hokkaido University, Sapporo, Hokkaido, Japan; Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Sapporo, Hokkaido, JapanFaculty of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, JapanDepartment of Chemistry, Faculty of Science, Hokkaido University, Sapporo, Hokkaido, Japan; Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Sapporo, Hokkaido, JapanLaboratory of Bioanalysis and Molecular Imaging, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, Japan; Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Sapporo, Hokkaido, Japan; Corresponding author at: Laboratory of Bioanalysis and Molecular Imaging, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido 060-0812, Japan.Near-infrared photoimmunotherapy (NIR-PIT) is a recently described method for cancer treatment that utilizes an antibody-conjugated phthalocyanine photosensitizer and NIR light. In NIR-PIT, light of 690 nm wavelength is used to activate a photosensitizer, IR700, while longer-wavelength light penetrates deeper into tissues. Thus, more effective NIR-PIT would be achieved by using photosensitizers that are activated by longer-wavelength light. The absorption wavelength would be red-shifted by destabilizing the highest occupied molecular orbital (HOMO) energy level by introducing electron donating groups at the α positions of a phthalocyanine ring. In this study, we developed a red-shifted photosensitizer for NIR-PIT, KA800, whose absorption wavelength was red-shifted by the introduction of ethoxy groups to IR700. As intended, the absorption maximum of KA800 was red-shifted compared to IR700 by 84 nm. Although phototoxicity of the antibody-KA800 (Ab-KA800) conjugate was observed in cultured cancer cells, no therapeutic effect was observed in mice. This is because the cytotoxicity of Ab-KA800 was mainly due to singlet oxygen, which can be quenched by abundant antioxidants in vivo. KA800 had low reactivity with respect to axial ligand cleavage required for inducing cell death via aggregate formation, a unique cytotoxic mechanism in NIR-PIT. The axial ligand cleavage proceeds via the anion radical formation of the photosensitizer, and KA800 was found to be less likely to receive an electron than IR700. This may be due to the destabilization of the HOMO energy level of KA800. Therefore, our findings suggest that stabilizing the lowest unoccupied molecular orbital (LUMO) energy level would be better than destabilizing the HOMO energy level for developing a red-shifted photosensitizer for NIR-PIT.http://www.sciencedirect.com/science/article/pii/S2666469024000058Antibody conjugateAxial ligandNear-infrared photoimmunotherapyPhotosensitizerRed shiftSilicon phthalocyanine |
| spellingShingle | Yuto Goto Kanta Ando Hideo Takakura Kohei Nakajima Masato Kobayashi Osamu Inanami Tetsuya Taketsugu Mikako Ogawa Development of a red-shifted photosensitizer for near-infrared photoimmunotherapy of cancer Journal of Photochemistry and Photobiology Antibody conjugate Axial ligand Near-infrared photoimmunotherapy Photosensitizer Red shift Silicon phthalocyanine |
| title | Development of a red-shifted photosensitizer for near-infrared photoimmunotherapy of cancer |
| title_full | Development of a red-shifted photosensitizer for near-infrared photoimmunotherapy of cancer |
| title_fullStr | Development of a red-shifted photosensitizer for near-infrared photoimmunotherapy of cancer |
| title_full_unstemmed | Development of a red-shifted photosensitizer for near-infrared photoimmunotherapy of cancer |
| title_short | Development of a red-shifted photosensitizer for near-infrared photoimmunotherapy of cancer |
| title_sort | development of a red shifted photosensitizer for near infrared photoimmunotherapy of cancer |
| topic | Antibody conjugate Axial ligand Near-infrared photoimmunotherapy Photosensitizer Red shift Silicon phthalocyanine |
| url | http://www.sciencedirect.com/science/article/pii/S2666469024000058 |
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