Investigating the Tumor-Suppressive, Antioxidant Effects and Molecular Binding Affinity of Quercetin-Loaded Selenium Nanoparticles in Breast Cancer Cells

Abstract In 2023, breast cancer is expected to have nearly 2 million new cases, making it the second most common cancer overall and the most prevalent among women. Multidrug resistance limits the effectiveness of chemotherapy; however, quercetin, a natural flavonoid, helps combat this issue. The goal of the current investigation is to determine the impact of a novel composite of quercetin and selenium nanoparticles (SeNPs) on the breast cancer cell lines MDA-MB-231 and MCF-7 in order to enhance quercetin’s tumor-suppressive action and decrease selenium (Se) toxicity. Particle size, zeta potential, FTIR, SEM, UV–VIS spectroscopy, and EDX were used to characterize quercetin-selenium nanoparticles (Que-SeNPs), in addition to evaluation of the antioxidant, apoptotic, and anticancer properties. Moreover, autophagy (Atg-13) protein receptors and PD-1/PD-L1 checkpoint were targeted using molecular docking modeling and molecular dynamics (MD) simulations to assess the interaction stability between Que-SeNPs and three targets: PDL-1, PD-1, and Atg-13 HORMA domain. Que-SeNPs, synthesized with quercetin, were stable, semi-spherical (80–117 nm), and had a zeta potential of − 37.8 mV. They enhanced cytotoxicity, antioxidant activity, and apoptosis compared to quercetin alone in MCF-7 and MDA-MB-231 cells. Docking simulations showed strong binding to the PD-1/PD-L1 checkpoint and Atg-13 HORMA protein receptors. Moreover, the molecular dynamics simulation revealed that the behavior of the PD-L1 intriguing insights into its structural dynamics, therefore, suggesting a stable phase where the complex is adjusting to the simulation environment. The present data confirmed that the stable formula of Que-SeNPs is cytotoxic, antioxidant, and has a potential activity to increase apoptosis in breast cancer cells, with the potential to inhibit PD-1/PD-L1 and Atg-13 proteins. Graphical Abstract Role of Que-SeNPs on breast cancer cells in vitro against two breast cancer cell lines MDA-MB-231 and MCF-7.