Combinatorial Effects of Free and Nanoencapsulated Forms of Cabazitaxel and RAS-Selective Lethal 3 in Breast Cancer Cells
<b>Background:</b> Combination therapies for cancer have gained considerable attention due to their potential for enhancing therapeutic efficacy and decreasing drug resistance. Introducing nanodrug delivery systems in this context may further improve the therapy due to targeted delivery,...
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2025-05-01
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| author | Remya Valsalakumari Marek Feith Solveig Pettersen Andreas K. O. Åslund Ýrr Mørch Tore Skotland Kirsten Sandvig Gunhild Mari Mælandsmo Tore-Geir Iversen |
| author_facet | Remya Valsalakumari Marek Feith Solveig Pettersen Andreas K. O. Åslund Ýrr Mørch Tore Skotland Kirsten Sandvig Gunhild Mari Mælandsmo Tore-Geir Iversen |
| author_sort | Remya Valsalakumari |
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| description | <b>Background:</b> Combination therapies for cancer have gained considerable attention due to their potential for enhancing therapeutic efficacy and decreasing drug resistance. Introducing nanodrug delivery systems in this context may further improve the therapy due to targeted delivery, improved drug stability, sustained drug release, and prevention of rapid clearance from circulation. This study evaluates the combinatorial effects of two cytotoxic drugs, cabazitaxel (CBZ) and RSL3 (RAS-selective lethal 3), in free form as well as encapsulated within poly(2-ethyl butyl cyanoacrylate) (PEBCA) nanoparticles (NPs) in breast cancer cell lines. <b>Methods</b>: Cell proliferation was assessed using IncuCyte technology, and synergistic drug effects were determined with SynergyFinder Plus. Cell viability was measured with the MTT assay. Additionally, we investigated whether the combinatorial effects were reflected in alterations of metabolic activity or reactive oxygen species (ROS) production using Seahorse technology and the CM-H<sub>2</sub>DCFDA assay, respectively. <b>Results</b>: The data presented reveal, for the first time, that CBZ and RSL3 exhibit synergistically or additively combinatorial effects on various breast cancer cell lines. The pattern of cytotoxic effects was consistent, whether the drugs were in free form or encapsulated in NPs. Moreover, the combinatorial effects were not observed to be associated with early changes in metabolic activity or ROS production. <b>Conclusion</b>: This study highlights the potential of CBZ and RSL3 in combinatorial nanomedicine as they may act synergistically. Further studies are warranted to better understand the mechanisms behind these combinatorial effects. |
| format | Article |
| id | doaj-art-e5cc013f185e4ac39fd4a0c946e4993d |
| institution | Kabale University |
| issn | 1999-4923 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj-art-e5cc013f185e4ac39fd4a0c946e4993d2025-08-20T03:47:57ZengMDPI AGPharmaceutics1999-49232025-05-0117565710.3390/pharmaceutics17050657Combinatorial Effects of Free and Nanoencapsulated Forms of Cabazitaxel and RAS-Selective Lethal 3 in Breast Cancer CellsRemya Valsalakumari0Marek Feith1Solveig Pettersen2Andreas K. O. Åslund3Ýrr Mørch4Tore Skotland5Kirsten Sandvig6Gunhild Mari Mælandsmo7Tore-Geir Iversen8Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, 0379 Oslo, NorwayDepartment of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, 0379 Oslo, NorwayDepartment of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, 0379 Oslo, NorwayDepartment of Biotechnology and Nanomedicine, SINTEF AS, 7034 Trondheim, NorwayDepartment of Biotechnology and Nanomedicine, SINTEF AS, 7034 Trondheim, NorwayDepartment of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, 0379 Oslo, NorwayDepartment of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, 0379 Oslo, NorwayDepartment of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, 0379 Oslo, NorwayDepartment of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, 0379 Oslo, Norway<b>Background:</b> Combination therapies for cancer have gained considerable attention due to their potential for enhancing therapeutic efficacy and decreasing drug resistance. Introducing nanodrug delivery systems in this context may further improve the therapy due to targeted delivery, improved drug stability, sustained drug release, and prevention of rapid clearance from circulation. This study evaluates the combinatorial effects of two cytotoxic drugs, cabazitaxel (CBZ) and RSL3 (RAS-selective lethal 3), in free form as well as encapsulated within poly(2-ethyl butyl cyanoacrylate) (PEBCA) nanoparticles (NPs) in breast cancer cell lines. <b>Methods</b>: Cell proliferation was assessed using IncuCyte technology, and synergistic drug effects were determined with SynergyFinder Plus. Cell viability was measured with the MTT assay. Additionally, we investigated whether the combinatorial effects were reflected in alterations of metabolic activity or reactive oxygen species (ROS) production using Seahorse technology and the CM-H<sub>2</sub>DCFDA assay, respectively. <b>Results</b>: The data presented reveal, for the first time, that CBZ and RSL3 exhibit synergistically or additively combinatorial effects on various breast cancer cell lines. The pattern of cytotoxic effects was consistent, whether the drugs were in free form or encapsulated in NPs. Moreover, the combinatorial effects were not observed to be associated with early changes in metabolic activity or ROS production. <b>Conclusion</b>: This study highlights the potential of CBZ and RSL3 in combinatorial nanomedicine as they may act synergistically. Further studies are warranted to better understand the mechanisms behind these combinatorial effects.https://www.mdpi.com/1999-4923/17/5/657cabazitaxelRSL3combinatorial effectsbreast cancerpoly(2-ethyl butyl cyanoacrylate)nanoparticles |
| spellingShingle | Remya Valsalakumari Marek Feith Solveig Pettersen Andreas K. O. Åslund Ýrr Mørch Tore Skotland Kirsten Sandvig Gunhild Mari Mælandsmo Tore-Geir Iversen Combinatorial Effects of Free and Nanoencapsulated Forms of Cabazitaxel and RAS-Selective Lethal 3 in Breast Cancer Cells Pharmaceutics cabazitaxel RSL3 combinatorial effects breast cancer poly(2-ethyl butyl cyanoacrylate) nanoparticles |
| title | Combinatorial Effects of Free and Nanoencapsulated Forms of Cabazitaxel and RAS-Selective Lethal 3 in Breast Cancer Cells |
| title_full | Combinatorial Effects of Free and Nanoencapsulated Forms of Cabazitaxel and RAS-Selective Lethal 3 in Breast Cancer Cells |
| title_fullStr | Combinatorial Effects of Free and Nanoencapsulated Forms of Cabazitaxel and RAS-Selective Lethal 3 in Breast Cancer Cells |
| title_full_unstemmed | Combinatorial Effects of Free and Nanoencapsulated Forms of Cabazitaxel and RAS-Selective Lethal 3 in Breast Cancer Cells |
| title_short | Combinatorial Effects of Free and Nanoencapsulated Forms of Cabazitaxel and RAS-Selective Lethal 3 in Breast Cancer Cells |
| title_sort | combinatorial effects of free and nanoencapsulated forms of cabazitaxel and ras selective lethal 3 in breast cancer cells |
| topic | cabazitaxel RSL3 combinatorial effects breast cancer poly(2-ethyl butyl cyanoacrylate) nanoparticles |
| url | https://www.mdpi.com/1999-4923/17/5/657 |
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