Dendritic Cells Pulsed with Tumor Lysates Induced by Tetracyanotetra(aryl)porphyrazines-Based Photodynamic Therapy Effectively Trigger Anti-Tumor Immunity in an Orthotopic Mouse Glioma Model
Research in the past decade on immunogenic cell death (ICD) has shown that the immunogenicity of dying tumor cells is crucial for effective anticancer therapy. ICD induction leads to the emission of specific damage-associated molecular patterns (DAMPs), which act as danger signals and as adjuvants t...
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| Format: | Article |
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MDPI AG
2023-10-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/10/2430 |
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| author | Tikhon S. Redkin Ekaterina E. Sleptsova Victoria D. Turubanova Mariia O. Saviuk Svetlana A. Lermontova Larisa G. Klapshina Nina N. Peskova Irina V. Balalaeva Olga Krysko Tatiana A. Mishchenko Maria V. Vedunova Dmitri V. Krysko |
| author_facet | Tikhon S. Redkin Ekaterina E. Sleptsova Victoria D. Turubanova Mariia O. Saviuk Svetlana A. Lermontova Larisa G. Klapshina Nina N. Peskova Irina V. Balalaeva Olga Krysko Tatiana A. Mishchenko Maria V. Vedunova Dmitri V. Krysko |
| author_sort | Tikhon S. Redkin |
| collection | DOAJ |
| description | Research in the past decade on immunogenic cell death (ICD) has shown that the immunogenicity of dying tumor cells is crucial for effective anticancer therapy. ICD induction leads to the emission of specific damage-associated molecular patterns (DAMPs), which act as danger signals and as adjuvants to activate specific anti-tumor immune responses, leading to the elimination of tumor cells and the formation of long-term immunological memory. ICD can be triggered by many anticancer treatment modalities, including photodynamic therapy (PDT). However, due to the variety of photosensitizers used and the lack of a universally adopted PDT protocol, there is a need to develop novel PDT with a proven ICD capability. In the present study, we characterized the abilities of two photoactive dyes to induce ICD in experimental glioma in vitro and in vivo. One dye was from the tetracyanotetra(aryl)porphyrazine group with 9-phenanthrenyl (<b>pz I</b>), and the other was from the 4-(4-fluorobenzyoxy)phenyl (<b>pz III</b>) group in the aryl frame of the macrocycle. We showed that after the photosensitizers penetrated into murine glioma GL261 cells, they localized predominantly in the Golgi apparatus and partially in the endoplasmic reticulum, providing efficient phototoxic activity against glioma GL261 cells upon light irradiation at a dose of 20 J/cm<sup>2</sup> (λex 630 nm; 20 mW/cm<sup>2</sup>). We demonstrated that <b>pz I</b>-PDT and <b>pz III</b>-PDT can act as efficient ICD inducers when applied to glioma GL261 cells, facilitating the release of two crucial DAMPs (ATP and HMGB1). Moreover, glioma GL261 cells stimulated with <b>pz I</b>-PDT or <b>pz III</b>-PDT provided strong protection against tumor growth in a prophylactic subcutaneous glioma vaccination model. Finally, we showed that dendritic cell (DC) vaccines pulsed with the lysates of glioma GL261 cells pre-treated with <b>pz-I</b>-PDT or <b>pz-III</b>-PDT could act as effective inducers of adaptive anti-tumor immunity in an intracranial orthotopic glioma mouse model. |
| first_indexed | 2024-03-10T20:58:29Z |
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| id | doaj.art-314193d9eefd4e6b8210e90a43c89af4 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T20:58:29Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-314193d9eefd4e6b8210e90a43c89af42023-11-19T17:44:24ZengMDPI AGPharmaceutics1999-49232023-10-011510243010.3390/pharmaceutics15102430Dendritic Cells Pulsed with Tumor Lysates Induced by Tetracyanotetra(aryl)porphyrazines-Based Photodynamic Therapy Effectively Trigger Anti-Tumor Immunity in an Orthotopic Mouse Glioma ModelTikhon S. Redkin0Ekaterina E. Sleptsova1Victoria D. Turubanova2Mariia O. Saviuk3Svetlana A. Lermontova4Larisa G. Klapshina5Nina N. Peskova6Irina V. Balalaeva7Olga Krysko8Tatiana A. Mishchenko9Maria V. Vedunova10Dmitri V. Krysko11Institute of Neurosciences, National Research Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, RussiaInstitute of Neurosciences, National Research Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, RussiaInstitute of Neurosciences, National Research Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, RussiaInstitute of Neurosciences, National Research Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, RussiaSector of Chromophors for Medicine, G.A. Razuvaev Institute of Organometallic Chemistry of the Russian Academy of Sciences, 49 Tropinin St., 603137 Nizhny Novgorod, RussiaSector of Chromophors for Medicine, G.A. Razuvaev Institute of Organometallic Chemistry of the Russian Academy of Sciences, 49 Tropinin St., 603137 Nizhny Novgorod, RussiaInstitute of Biology and Biomedicine, National Research Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, RussiaInstitute of Biology and Biomedicine, National Research Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, RussiaCell Death Investigation and Therapy Laboratory, Anatomy and Embryology Unit, Department of Human Structure and Repair, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, BelgiumInstitute of Biology and Biomedicine, National Research Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, RussiaInstitute of Biology and Biomedicine, National Research Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, RussiaCell Death Investigation and Therapy Laboratory, Anatomy and Embryology Unit, Department of Human Structure and Repair, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, BelgiumResearch in the past decade on immunogenic cell death (ICD) has shown that the immunogenicity of dying tumor cells is crucial for effective anticancer therapy. ICD induction leads to the emission of specific damage-associated molecular patterns (DAMPs), which act as danger signals and as adjuvants to activate specific anti-tumor immune responses, leading to the elimination of tumor cells and the formation of long-term immunological memory. ICD can be triggered by many anticancer treatment modalities, including photodynamic therapy (PDT). However, due to the variety of photosensitizers used and the lack of a universally adopted PDT protocol, there is a need to develop novel PDT with a proven ICD capability. In the present study, we characterized the abilities of two photoactive dyes to induce ICD in experimental glioma in vitro and in vivo. One dye was from the tetracyanotetra(aryl)porphyrazine group with 9-phenanthrenyl (<b>pz I</b>), and the other was from the 4-(4-fluorobenzyoxy)phenyl (<b>pz III</b>) group in the aryl frame of the macrocycle. We showed that after the photosensitizers penetrated into murine glioma GL261 cells, they localized predominantly in the Golgi apparatus and partially in the endoplasmic reticulum, providing efficient phototoxic activity against glioma GL261 cells upon light irradiation at a dose of 20 J/cm<sup>2</sup> (λex 630 nm; 20 mW/cm<sup>2</sup>). We demonstrated that <b>pz I</b>-PDT and <b>pz III</b>-PDT can act as efficient ICD inducers when applied to glioma GL261 cells, facilitating the release of two crucial DAMPs (ATP and HMGB1). Moreover, glioma GL261 cells stimulated with <b>pz I</b>-PDT or <b>pz III</b>-PDT provided strong protection against tumor growth in a prophylactic subcutaneous glioma vaccination model. Finally, we showed that dendritic cell (DC) vaccines pulsed with the lysates of glioma GL261 cells pre-treated with <b>pz-I</b>-PDT or <b>pz-III</b>-PDT could act as effective inducers of adaptive anti-tumor immunity in an intracranial orthotopic glioma mouse model.https://www.mdpi.com/1999-4923/15/10/2430ICDphotosensitizersGL261DAMPsATPHMGB1 |
| spellingShingle | Tikhon S. Redkin Ekaterina E. Sleptsova Victoria D. Turubanova Mariia O. Saviuk Svetlana A. Lermontova Larisa G. Klapshina Nina N. Peskova Irina V. Balalaeva Olga Krysko Tatiana A. Mishchenko Maria V. Vedunova Dmitri V. Krysko Dendritic Cells Pulsed with Tumor Lysates Induced by Tetracyanotetra(aryl)porphyrazines-Based Photodynamic Therapy Effectively Trigger Anti-Tumor Immunity in an Orthotopic Mouse Glioma Model Pharmaceutics ICD photosensitizers GL261 DAMPs ATP HMGB1 |
| title | Dendritic Cells Pulsed with Tumor Lysates Induced by Tetracyanotetra(aryl)porphyrazines-Based Photodynamic Therapy Effectively Trigger Anti-Tumor Immunity in an Orthotopic Mouse Glioma Model |
| title_full | Dendritic Cells Pulsed with Tumor Lysates Induced by Tetracyanotetra(aryl)porphyrazines-Based Photodynamic Therapy Effectively Trigger Anti-Tumor Immunity in an Orthotopic Mouse Glioma Model |
| title_fullStr | Dendritic Cells Pulsed with Tumor Lysates Induced by Tetracyanotetra(aryl)porphyrazines-Based Photodynamic Therapy Effectively Trigger Anti-Tumor Immunity in an Orthotopic Mouse Glioma Model |
| title_full_unstemmed | Dendritic Cells Pulsed with Tumor Lysates Induced by Tetracyanotetra(aryl)porphyrazines-Based Photodynamic Therapy Effectively Trigger Anti-Tumor Immunity in an Orthotopic Mouse Glioma Model |
| title_short | Dendritic Cells Pulsed with Tumor Lysates Induced by Tetracyanotetra(aryl)porphyrazines-Based Photodynamic Therapy Effectively Trigger Anti-Tumor Immunity in an Orthotopic Mouse Glioma Model |
| title_sort | dendritic cells pulsed with tumor lysates induced by tetracyanotetra aryl porphyrazines based photodynamic therapy effectively trigger anti tumor immunity in an orthotopic mouse glioma model |
| topic | ICD photosensitizers GL261 DAMPs ATP HMGB1 |
| url | https://www.mdpi.com/1999-4923/15/10/2430 |
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