Combinatorial Effects of Free and Nanoencapsulated Forms of Cabazitaxel and RAS-Selective Lethal 3 in Breast Cancer Cells
Permanent lenke
https://hdl.handle.net/10037/37183Dato
2025-05-17Type
Journal articleTidsskriftartikkel
Peer reviewed
Forfatter
Vasalakumari, Remya; Feith, Marek; Pettersen, Solveig; Åslund, Andreas K. O.; Mørch, Ýrr; Skotland, Tore; Sandvig, Kirsten; Mælandsmo, Gunhild Mari; Iversen, Tore GeirSammendrag
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.
Forlag
MDPISitering
Vasalakumari, Feith M, Pettersen S, Åslund AKO, Mørch Ý, Skotland T, Sandvig K, Mælandsmo GM, Iversen TG. Combinatorial Effects of Free and Nanoencapsulated Forms of Cabazitaxel and RAS-Selective Lethal 3 in Breast Cancer Cells. Pharmaceutics. 2025;17(5):657Metadata
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