Effective inhibition of breast cancer stem cell properties by quercetin-loaded solid lipid nanoparticles via reduction of Smad2/Smad3 phosphorylation and β-catenin signaling pathway in triple-negative breast cancer.

Background: The presence of cancer stem cells (CSCs) is a major cause of resistance to cancer therapy and recurrence. Triple-negative breast cancer (TNBC) is a subtype that responds poorly to therapy, making it a significant global health issue. Quercetin (QC) has been shown to affect CSC viability, but its low bioavailability limits its clinical use. This study aims to increase the effectiveness of QC in inhibiting CSC generation by using solid lipid nanoparticles (SLNs) in MDA-MB231 cells.

Materials And Methods: After treating MCF-7 and MDA-MB231 cells with 18.9 μM and 13.4 μM of QC and QC-SLN for 48 h, respectively, cell viability, migration, sphere formation, protein expression of β-catenin, p-Smad 2 and 3, and gene expression of EMT and CSC markers were evaluated.

Results: The QC-SLN with particle size of 154 nm, zeta potential of -27.7 mV, and encapsulation efficacy of 99.6% was found to be the most effective. Compared to QC, QC-SLN significantly reduced cell viability, migration, sphere formation, protein expression of β-catenin and p-Smad 2 and 3, and gene expression of CD, zinc finger E-box binding homeobox 1 (ZEB1), vimentin, while increasing the gene expression of E-cadherin.

Conclusions: Our findings demonstrate that SLNs improve the cytotoxic effect of QC in MDA-MB231 cells by increasing its bioavailability and inhibiting epithelial-mesenchymal transition (EMT), thereby effectively inhibiting CSC generation. Therefore, SLNs could be a promising new treatment for TNBC, but more in vivo studies are needed to confirm their efficacy.