Lipid-based nanocarriers co-loaded with artemether and triglycerides of docosahexaenoic acid: Effects on human breast cancer cells - 17/01/21
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Graphical abstract |
Highlights |
• | Lipid-nanocarriers improve the activity of artemether and DHA in human breast cancer cells. |
• | Artemether and docosahexaenoic acid increased the antitumor effect on breast cancer cells. |
• | Artemether and fish oil in lipid-based nanocarriers is active against breast cancer. |
• | The activity of artemether and fish oil combination in human breast cancer cells. |
• | Human breast cancer cells are more sensitive to artemether and fish oil combination. |
Abstract |
Artemether (ART) was combined with triglyceride of docosahexaenoic acid (DHA) as the lipid-core in nanoemulsions (NE), nanostructured lipid carriers (NLC), and PEG-PLA nanocapsules (NC) formulations, and their effects on human breast cancer cells were evaluated. ART has been extensively used for malaria and has also therapeutic potential against different tumor cells in a repositioning strategy. The concentration-dependent cytotoxicity in vitro was determined in tumor lineages, MDA-MB-231 and MCF-7, and non-tumor MCF-10A cells for free-ART/DHA combination and its formulations. The cells were monitored for viability, effects on cell migration and clonogenicity, cell death mechanism, and qualitative and quantitative cell uptake of nanocarriers. The lipid-nanocarriers showed mean sizes over the range of 110 and 280 nm with monodisperse populations and zeta potential values ranging from −21 to −67 mV. The ART encapsulation efficiencies varied from 57 to 83 %. ART/DHA co-loaded in three different lipid nanocarriers reduced the MDA-MB-231 and MCF-7 viability in a dose-dependent manner with enhanced selectivity toward tumor cell lines. They also reduced clonogenicity and the ability of cells to migrate showing antimetastatic potential in both cell lines and triggered apoptosis in MCF-7 cells. Confocal microscopy and flow cytometry analysis showed that NC, NLC, and NE were rapidly internalized by cells, with higher interaction displayed by NE with MCF-7 cells compared to NC and NLC that was correlated with the strongest NE-fluorescence in cells. Therefore, this study not only demonstrated the value of this new combination of ART/DHA as a new strategy for breast cancer therapy but also showed enhanced cytotoxicity and potential metastatic activity of lipid-based formulations against human breast cancer cells that indicate great potential for pre-clinical and clinical translation.
Le texte complet de cet article est disponible en PDF.Keywords : Breast cancer, Nanocapsule, Nanoemulsion, Nanostructured lipid carrier, Artemether, Docosahexaenoic acid
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Vol 134
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