Cellular Uptake and Phototoxicity Optimization of Arene Ruthenium Porphyrin Derivatives
In this study, dinuclear and tetranuclear arene ruthenium porphyrins were synthesized and assessed for their potential as photosensitizers (PSs) in photodynamic therapy (PDT) using the Colo205 colon cancer cell line as a model system. Reactive oxygen species (ROS) production, cellular uptake, impact...
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MDPI AG
2024-03-01
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| Series: | Inorganics |
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| Online Access: | https://www.mdpi.com/2304-6740/12/3/86 |
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| author | Zeinab Janbeih Manuel Gallardo-Villagrán Bruno Therrien Mona Diab-Assaf Bertrand Liagre Ludmil Benov |
| author_facet | Zeinab Janbeih Manuel Gallardo-Villagrán Bruno Therrien Mona Diab-Assaf Bertrand Liagre Ludmil Benov |
| author_sort | Zeinab Janbeih |
| collection | DOAJ |
| description | In this study, dinuclear and tetranuclear arene ruthenium porphyrins were synthesized and assessed for their potential as photosensitizers (PSs) in photodynamic therapy (PDT) using the Colo205 colon cancer cell line as a model system. Reactive oxygen species (ROS) production, cellular uptake, impact on cell viability, and mechanisms of cell death induced by the synthesized compounds were comprehensively investigated. Our results revealed that the number of arene ruthenium units, as well as zinc (Zn) metalation of the porphyrin core, significantly influenced ROS production and increased it two-folds compared to the Zn-free analogs. The uptake of tetra-substituted Zn-porphyrins by the cancer cells increased to 2.8 nmol/10<sup>6</sup> cells compared to 0.6 nmol/10<sup>6</sup> cells of the disubstituted Zn-free and Zn-chelating porphyrins. The anticancer photo-activity of the complexes, where the percentage of metabolic activity of disubstituted Zn-porphyrins decreased to 26% when Zn was inserted, was compared to disubstituted Zn-free analogs. A further decrease in metabolic activity was observed, when the number of arene ruthenium units increased in the tetra-substituted Zn-porphyrins and tetra-substituted Zn-free compounds, reaching 4% and 14% respectively. Moreover, the percentage of apoptotic cell deaths increased to 40% when Zn was inserted into disubstituted porphyrins, compared to disubstituted Zn-free analog, and 50% when the number of arene ruthenium units increased. Overall, the tetra-substituted Zn chelating porphyrins exhibited the highest PDT efficiency, followed by the di-substituted Zn-porphyrins. These findings underscore the importance of structural design in optimizing the efficacy of arene ruthenium porphyrins as PSs for PDT, offering valuable insights for the development of targeted cancer therapeutics. |
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| language | English |
| last_indexed | 2024-04-24T18:10:23Z |
| publishDate | 2024-03-01 |
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| series | Inorganics |
| spelling | doaj.art-81db210954524ce7824ca716482646412024-03-27T13:47:08ZengMDPI AGInorganics2304-67402024-03-011238610.3390/inorganics12030086Cellular Uptake and Phototoxicity Optimization of Arene Ruthenium Porphyrin DerivativesZeinab Janbeih0Manuel Gallardo-Villagrán1Bruno Therrien2Mona Diab-Assaf3Bertrand Liagre4Ludmil Benov5Biochemistry Department, Faculty of Medicine, Kuwait University, Kuwait City 12037, KuwaitUniv. Limoges, LABCiS, UR 22722, Faculté de Pharmacie, F-87000 Limoges, FranceInstitut de Chimie, Université de Neuchâtel, Avenue de Bellevaux 51, CH-2000 Neuchâtel, SwitzerlandDoctoral School of Sciences and Technology, Lebanese University, Hadath, Beirut 21219, LebanonUniv. Limoges, LABCiS, UR 22722, Faculté de Pharmacie, F-87000 Limoges, FranceBiochemistry Department, Faculty of Medicine, Kuwait University, Kuwait City 12037, KuwaitIn this study, dinuclear and tetranuclear arene ruthenium porphyrins were synthesized and assessed for their potential as photosensitizers (PSs) in photodynamic therapy (PDT) using the Colo205 colon cancer cell line as a model system. Reactive oxygen species (ROS) production, cellular uptake, impact on cell viability, and mechanisms of cell death induced by the synthesized compounds were comprehensively investigated. Our results revealed that the number of arene ruthenium units, as well as zinc (Zn) metalation of the porphyrin core, significantly influenced ROS production and increased it two-folds compared to the Zn-free analogs. The uptake of tetra-substituted Zn-porphyrins by the cancer cells increased to 2.8 nmol/10<sup>6</sup> cells compared to 0.6 nmol/10<sup>6</sup> cells of the disubstituted Zn-free and Zn-chelating porphyrins. The anticancer photo-activity of the complexes, where the percentage of metabolic activity of disubstituted Zn-porphyrins decreased to 26% when Zn was inserted, was compared to disubstituted Zn-free analogs. A further decrease in metabolic activity was observed, when the number of arene ruthenium units increased in the tetra-substituted Zn-porphyrins and tetra-substituted Zn-free compounds, reaching 4% and 14% respectively. Moreover, the percentage of apoptotic cell deaths increased to 40% when Zn was inserted into disubstituted porphyrins, compared to disubstituted Zn-free analog, and 50% when the number of arene ruthenium units increased. Overall, the tetra-substituted Zn chelating porphyrins exhibited the highest PDT efficiency, followed by the di-substituted Zn-porphyrins. These findings underscore the importance of structural design in optimizing the efficacy of arene ruthenium porphyrins as PSs for PDT, offering valuable insights for the development of targeted cancer therapeutics.https://www.mdpi.com/2304-6740/12/3/86photodynamic therapyarene ruthenium complexesporphyrincolon cancerphotosensitizers |
| spellingShingle | Zeinab Janbeih Manuel Gallardo-Villagrán Bruno Therrien Mona Diab-Assaf Bertrand Liagre Ludmil Benov Cellular Uptake and Phototoxicity Optimization of Arene Ruthenium Porphyrin Derivatives Inorganics photodynamic therapy arene ruthenium complexes porphyrin colon cancer photosensitizers |
| title | Cellular Uptake and Phototoxicity Optimization of Arene Ruthenium Porphyrin Derivatives |
| title_full | Cellular Uptake and Phototoxicity Optimization of Arene Ruthenium Porphyrin Derivatives |
| title_fullStr | Cellular Uptake and Phototoxicity Optimization of Arene Ruthenium Porphyrin Derivatives |
| title_full_unstemmed | Cellular Uptake and Phototoxicity Optimization of Arene Ruthenium Porphyrin Derivatives |
| title_short | Cellular Uptake and Phototoxicity Optimization of Arene Ruthenium Porphyrin Derivatives |
| title_sort | cellular uptake and phototoxicity optimization of arene ruthenium porphyrin derivatives |
| topic | photodynamic therapy arene ruthenium complexes porphyrin colon cancer photosensitizers |
| url | https://www.mdpi.com/2304-6740/12/3/86 |
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