The Potential of Congo Red Supplied Aggregates of Multitargeted Tyrosine Kinase Inhibitor (Sorafenib, BAY-43-9006) in Enhancing Therapeutic Impact on Bladder Cancer
Bladder cancer is a common malignancy associated with high recurrence rates and potential progression to invasive forms. Sorafenib, a multi-targeted tyrosine kinase inhibitor, has shown promise in anti-cancer therapy, but its cytotoxicity to normal cells and aggregation in solution limits its clinic...
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| Format: | Article |
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MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/1/269 |
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| author | Małgorzata Lasota Daniel Jankowski Anna Wiśniewska Michał Sarna Marta Kaczor-Kamińska Anna Misterka Mateusz Szczepaniak Joanna Dulińska-Litewka Andrzej Górecki |
| author_facet | Małgorzata Lasota Daniel Jankowski Anna Wiśniewska Michał Sarna Marta Kaczor-Kamińska Anna Misterka Mateusz Szczepaniak Joanna Dulińska-Litewka Andrzej Górecki |
| author_sort | Małgorzata Lasota |
| collection | DOAJ |
| description | Bladder cancer is a common malignancy associated with high recurrence rates and potential progression to invasive forms. Sorafenib, a multi-targeted tyrosine kinase inhibitor, has shown promise in anti-cancer therapy, but its cytotoxicity to normal cells and aggregation in solution limits its clinical application. To address these challenges, we investigated the formation of supramolecular aggregates of sorafenib with Congo red (CR), a bis-azo dye known for its supramolecular interaction. We analyzed different mole ratios of CR-sorafenib aggregates and evaluated their effects on bladder cancer cells of varying levels of malignancy. In addition, we also evaluated the effect of the test compounds on normal uroepithelial cells. Our results demonstrated that sorafenib inhibits the proliferation of bladder cancer cells and induces apoptosis in a dose-dependent manner. However, high concentrations of sorafenib also showed cytotoxicity to normal uroepithelial cells. In contrast, the CR-BAY aggregates exhibited reduced cytotoxicity to normal cells while maintaining anti-cancer activity. The aggregates inhibited cancer cell migration and invasion, suggesting their potential for metastasis prevention. Dynamic light scattering and UV-VIS measurements confirmed the formation of stable co-aggregates with distinctive spectral properties. These CR-sorafenib aggregates may provide a promising approach to targeted therapy with reduced cytotoxicity and improved stability for drug delivery in bladder cancer treatment. This work shows that the drug-excipient aggregates proposed and described so far, as Congo red—sorafenib, can be a real step forward in anti-cancer therapies. |
| first_indexed | 2024-03-08T15:05:10Z |
| format | Article |
| id | doaj.art-4017ad3485874bd2ae2e86cc852d7ea7 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T15:05:10Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-4017ad3485874bd2ae2e86cc852d7ea72024-01-10T14:58:48ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0125126910.3390/ijms25010269The Potential of Congo Red Supplied Aggregates of Multitargeted Tyrosine Kinase Inhibitor (Sorafenib, BAY-43-9006) in Enhancing Therapeutic Impact on Bladder CancerMałgorzata Lasota0Daniel Jankowski1Anna Wiśniewska2Michał Sarna3Marta Kaczor-Kamińska4Anna Misterka5Mateusz Szczepaniak6Joanna Dulińska-Litewka7Andrzej Górecki8Chair of Medical Biochemistry, Jagiellonian University Medical College, Kopernika 7, 31-034 Krakow, PolandSSG of Targeted Therapy and Supramolecular Systems, Jagiellonian University Medical College, Kopernika 7, 31-034 Krakow, PolandChair of Pharmacology, Faculty of Medicine, Jagiellonian University Medical College, Grzegórzecka 16, 31-531 Krakow, PolandDepartment of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, PolandChair of Medical Biochemistry, Jagiellonian University Medical College, Kopernika 7, 31-034 Krakow, PolandChair of Medical Biochemistry, Jagiellonian University Medical College, Kopernika 7, 31-034 Krakow, PolandSSG of Targeted Therapy and Supramolecular Systems, Jagiellonian University Medical College, Kopernika 7, 31-034 Krakow, PolandChair of Medical Biochemistry, Jagiellonian University Medical College, Kopernika 7, 31-034 Krakow, PolandDepartment of Physical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, PolandBladder cancer is a common malignancy associated with high recurrence rates and potential progression to invasive forms. Sorafenib, a multi-targeted tyrosine kinase inhibitor, has shown promise in anti-cancer therapy, but its cytotoxicity to normal cells and aggregation in solution limits its clinical application. To address these challenges, we investigated the formation of supramolecular aggregates of sorafenib with Congo red (CR), a bis-azo dye known for its supramolecular interaction. We analyzed different mole ratios of CR-sorafenib aggregates and evaluated their effects on bladder cancer cells of varying levels of malignancy. In addition, we also evaluated the effect of the test compounds on normal uroepithelial cells. Our results demonstrated that sorafenib inhibits the proliferation of bladder cancer cells and induces apoptosis in a dose-dependent manner. However, high concentrations of sorafenib also showed cytotoxicity to normal uroepithelial cells. In contrast, the CR-BAY aggregates exhibited reduced cytotoxicity to normal cells while maintaining anti-cancer activity. The aggregates inhibited cancer cell migration and invasion, suggesting their potential for metastasis prevention. Dynamic light scattering and UV-VIS measurements confirmed the formation of stable co-aggregates with distinctive spectral properties. These CR-sorafenib aggregates may provide a promising approach to targeted therapy with reduced cytotoxicity and improved stability for drug delivery in bladder cancer treatment. This work shows that the drug-excipient aggregates proposed and described so far, as Congo red—sorafenib, can be a real step forward in anti-cancer therapies.https://www.mdpi.com/1422-0067/25/1/269bladder cancertyrosine kinases inhibitorCongo redpersonalized medicinemultidisciplinary treatment |
| spellingShingle | Małgorzata Lasota Daniel Jankowski Anna Wiśniewska Michał Sarna Marta Kaczor-Kamińska Anna Misterka Mateusz Szczepaniak Joanna Dulińska-Litewka Andrzej Górecki The Potential of Congo Red Supplied Aggregates of Multitargeted Tyrosine Kinase Inhibitor (Sorafenib, BAY-43-9006) in Enhancing Therapeutic Impact on Bladder Cancer International Journal of Molecular Sciences bladder cancer tyrosine kinases inhibitor Congo red personalized medicine multidisciplinary treatment |
| title | The Potential of Congo Red Supplied Aggregates of Multitargeted Tyrosine Kinase Inhibitor (Sorafenib, BAY-43-9006) in Enhancing Therapeutic Impact on Bladder Cancer |
| title_full | The Potential of Congo Red Supplied Aggregates of Multitargeted Tyrosine Kinase Inhibitor (Sorafenib, BAY-43-9006) in Enhancing Therapeutic Impact on Bladder Cancer |
| title_fullStr | The Potential of Congo Red Supplied Aggregates of Multitargeted Tyrosine Kinase Inhibitor (Sorafenib, BAY-43-9006) in Enhancing Therapeutic Impact on Bladder Cancer |
| title_full_unstemmed | The Potential of Congo Red Supplied Aggregates of Multitargeted Tyrosine Kinase Inhibitor (Sorafenib, BAY-43-9006) in Enhancing Therapeutic Impact on Bladder Cancer |
| title_short | The Potential of Congo Red Supplied Aggregates of Multitargeted Tyrosine Kinase Inhibitor (Sorafenib, BAY-43-9006) in Enhancing Therapeutic Impact on Bladder Cancer |
| title_sort | potential of congo red supplied aggregates of multitargeted tyrosine kinase inhibitor sorafenib bay 43 9006 in enhancing therapeutic impact on bladder cancer |
| topic | bladder cancer tyrosine kinases inhibitor Congo red personalized medicine multidisciplinary treatment |
| url | https://www.mdpi.com/1422-0067/25/1/269 |
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