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Pharmaceutics
Volume 17
Issue 5
10.3390/pharmaceutics17050657
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Combinatorial Effects of Free and Nanoencapsulated Forms of Cabazitaxel and RAS-Selective Lethal 3 in Breast Cancer Cells

by
Remya Valsalakumari
1,2,†,
Marek Feith
1,3,†,
Solveig Pettersen
1,
Andreas K. O. Åslund
4,
Ýrr Mørch
4,5,
Tore Skotland
2,6,
Kirsten Sandvig
2,6,7,
Gunhild Mari Mælandsmo
1,8 and
Tore-Geir Iversen
2,6,*
1
Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, 0379 Oslo, Norway
2
Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, 0379 Oslo, Norway
3
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0379 Oslo, Norway
4
Department of Biotechnology and Nanomedicine, SINTEF AS, 7034 Trondheim, Norway
5
NaDeNo Nanoscience AS, 7051 Trondheim, Norway
6
Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, 0379 Oslo, Norway
7
Department of Biosciences, University of Oslo, 0316 Oslo, Norway
8
Department of Medical Biology, University of Tromsø, 9019 Tromsø, Norway
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Pharmaceutics 2025, 17(5), 657; https://doi.org/10.3390/pharmaceutics17050657 (registering DOI)
Submission received: 10 April 2025 / Revised: 14 May 2025 / Accepted: 14 May 2025 / Published: 17 May 2025
(This article belongs to the Special Issue Nanoparticle-Mediated Targeted Drug Delivery Systems)
Versions Notes

Abstract

Background: 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. Methods: 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-H2DCFDA assay, respectively. Results: 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. Conclusion: 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.
Keywords: cabazitaxel; RSL3; combinatorial effects; breast cancer; poly(2-ethyl butyl cyanoacrylate); nanoparticles cabazitaxel; RSL3; combinatorial effects; breast cancer; poly(2-ethyl butyl cyanoacrylate); nanoparticles

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MDPI and ACS Style

Valsalakumari, R.; Feith, M.; Pettersen, S.; Åslund, A.K.O.; Mørch, Ý.; Skotland, T.; Sandvig, K.; Mælandsmo, G.M.; Iversen, T.-G. Combinatorial Effects of Free and Nanoencapsulated Forms of Cabazitaxel and RAS-Selective Lethal 3 in Breast Cancer Cells. Pharmaceutics 2025, 17, 657. https://doi.org/10.3390/pharmaceutics17050657

AMA Style

Valsalakumari R, Feith M, Pettersen S, Åslund AKO, Mørch Ý, Skotland T, Sandvig K, Mælandsmo GM, Iversen T-G. Combinatorial Effects of Free and Nanoencapsulated Forms of Cabazitaxel and RAS-Selective Lethal 3 in Breast Cancer Cells. Pharmaceutics. 2025; 17(5):657. https://doi.org/10.3390/pharmaceutics17050657

Chicago/Turabian Style

Valsalakumari, Remya, Marek Feith, Solveig Pettersen, Andreas K. O. Åslund, Ýrr Mørch, Tore Skotland, Kirsten Sandvig, Gunhild Mari Mælandsmo, and Tore-Geir Iversen. 2025. "Combinatorial Effects of Free and Nanoencapsulated Forms of Cabazitaxel and RAS-Selective Lethal 3 in Breast Cancer Cells" Pharmaceutics 17, no. 5: 657. https://doi.org/10.3390/pharmaceutics17050657

APA Style

Valsalakumari, R., Feith, M., Pettersen, S., Åslund, A. K. O., Mørch, Ý., Skotland, T., Sandvig, K., Mælandsmo, G. M., & Iversen, T.-G. (2025). Combinatorial Effects of Free and Nanoencapsulated Forms of Cabazitaxel and RAS-Selective Lethal 3 in Breast Cancer Cells. Pharmaceutics, 17(5), 657. https://doi.org/10.3390/pharmaceutics17050657

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