Feasibility of Photodynamic Therapy for Glioblastoma with the Mitochondria-Targeted Photosensitizer Tetramethylrhodamine Methyl Ester (TMRM)
One of the most challenging problems in the treatment of glioblastoma (GBM) is the highly infiltrative nature of the disease. Infiltrating cells that are non-resectable are left behind after debulking surgeries and become a source of regrowth and recurrence. To prevent tumor recurrence and increase...
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MDPI AG
2021-10-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/10/1453 |
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| author | Alex Vasilev Roba Sofi Stuart J. Smith Ruman Rahman Anja G. Teschemacher Sergey Kasparov |
| author_facet | Alex Vasilev Roba Sofi Stuart J. Smith Ruman Rahman Anja G. Teschemacher Sergey Kasparov |
| author_sort | Alex Vasilev |
| collection | DOAJ |
| description | One of the most challenging problems in the treatment of glioblastoma (GBM) is the highly infiltrative nature of the disease. Infiltrating cells that are non-resectable are left behind after debulking surgeries and become a source of regrowth and recurrence. To prevent tumor recurrence and increase patient survival, it is necessary to cleanse the adjacent tissue from GBM infiltrates. This requires an innovative local approach. One such approach is that of photodynamic therapy (PDT) which uses specific light-sensitizing agents called photosensitizers. Here, we show that tetramethylrhodamine methyl ester (TMRM), which has been used to asses mitochondrial potential, can be used as a photosensitizer to target GBM cells. Primary patient-derived GBM cell lines were used, including those specifically isolated from the infiltrative edge. PDT with TMRM using low-intensity green light induced mitochondrial damage, an irreversible drop in mitochondrial membrane potential and led to GBM cell death. Moreover, delayed photoactivation after TMRM loading selectively killed GBM cells but not cultured rat astrocytes. The efficacy of TMRM-PDT in certain GBM cell lines may be potentiated by adenylate cyclase activator NKH477. Together, these findings identify TMRM as a prototypical mitochondrially targeted photosensitizer with beneficial features which may be suitable for preclinical and clinical translation. |
| first_indexed | 2024-03-10T06:42:36Z |
| format | Article |
| id | doaj.art-9cb4c585491b4d7baa335ac18a07faca |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T06:42:36Z |
| publishDate | 2021-10-01 |
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| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-9cb4c585491b4d7baa335ac18a07faca2023-11-22T17:32:08ZengMDPI AGBiomedicines2227-90592021-10-01910145310.3390/biomedicines9101453Feasibility of Photodynamic Therapy for Glioblastoma with the Mitochondria-Targeted Photosensitizer Tetramethylrhodamine Methyl Ester (TMRM)Alex Vasilev0Roba Sofi1Stuart J. Smith2Ruman Rahman3Anja G. Teschemacher4Sergey Kasparov5School of Life Sciences, Immanuel Kant Baltic Federal University, Universitetskaya Str., 2, 236041 Kaliningrad, RussiaSchool of Physiology, Pharmacology and Neuroscience, University of Bristol, University Walk, Bristol BS8 1TD, UKChildren’s Brain Tumour Research Centre, Nottingham Biodiscovery Institute, School of Medicine, University of Nottingham, Nottingham NG7 2RD, UKChildren’s Brain Tumour Research Centre, Nottingham Biodiscovery Institute, School of Medicine, University of Nottingham, Nottingham NG7 2RD, UKSchool of Physiology, Pharmacology and Neuroscience, University of Bristol, University Walk, Bristol BS8 1TD, UKSchool of Life Sciences, Immanuel Kant Baltic Federal University, Universitetskaya Str., 2, 236041 Kaliningrad, RussiaOne of the most challenging problems in the treatment of glioblastoma (GBM) is the highly infiltrative nature of the disease. Infiltrating cells that are non-resectable are left behind after debulking surgeries and become a source of regrowth and recurrence. To prevent tumor recurrence and increase patient survival, it is necessary to cleanse the adjacent tissue from GBM infiltrates. This requires an innovative local approach. One such approach is that of photodynamic therapy (PDT) which uses specific light-sensitizing agents called photosensitizers. Here, we show that tetramethylrhodamine methyl ester (TMRM), which has been used to asses mitochondrial potential, can be used as a photosensitizer to target GBM cells. Primary patient-derived GBM cell lines were used, including those specifically isolated from the infiltrative edge. PDT with TMRM using low-intensity green light induced mitochondrial damage, an irreversible drop in mitochondrial membrane potential and led to GBM cell death. Moreover, delayed photoactivation after TMRM loading selectively killed GBM cells but not cultured rat astrocytes. The efficacy of TMRM-PDT in certain GBM cell lines may be potentiated by adenylate cyclase activator NKH477. Together, these findings identify TMRM as a prototypical mitochondrially targeted photosensitizer with beneficial features which may be suitable for preclinical and clinical translation.https://www.mdpi.com/2227-9059/9/10/1453glioblastomaphotodynamic therapyphotosensitizermitochondria |
| spellingShingle | Alex Vasilev Roba Sofi Stuart J. Smith Ruman Rahman Anja G. Teschemacher Sergey Kasparov Feasibility of Photodynamic Therapy for Glioblastoma with the Mitochondria-Targeted Photosensitizer Tetramethylrhodamine Methyl Ester (TMRM) Biomedicines glioblastoma photodynamic therapy photosensitizer mitochondria |
| title | Feasibility of Photodynamic Therapy for Glioblastoma with the Mitochondria-Targeted Photosensitizer Tetramethylrhodamine Methyl Ester (TMRM) |
| title_full | Feasibility of Photodynamic Therapy for Glioblastoma with the Mitochondria-Targeted Photosensitizer Tetramethylrhodamine Methyl Ester (TMRM) |
| title_fullStr | Feasibility of Photodynamic Therapy for Glioblastoma with the Mitochondria-Targeted Photosensitizer Tetramethylrhodamine Methyl Ester (TMRM) |
| title_full_unstemmed | Feasibility of Photodynamic Therapy for Glioblastoma with the Mitochondria-Targeted Photosensitizer Tetramethylrhodamine Methyl Ester (TMRM) |
| title_short | Feasibility of Photodynamic Therapy for Glioblastoma with the Mitochondria-Targeted Photosensitizer Tetramethylrhodamine Methyl Ester (TMRM) |
| title_sort | feasibility of photodynamic therapy for glioblastoma with the mitochondria targeted photosensitizer tetramethylrhodamine methyl ester tmrm |
| topic | glioblastoma photodynamic therapy photosensitizer mitochondria |
| url | https://www.mdpi.com/2227-9059/9/10/1453 |
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