Investigating the Tumor-Suppressive, Antioxidant Effects and Molecular Binding Affinity of Quercetin-Loaded Selenium Nanoparticles in Breast Cancer Cells
Nosibah Abdul-Razek, Rehab G. Khalil, Mahmoud Abdel‐Latif, Mahmoud M. Kamel, Ibrahim M. Alhazza, Ezzat M. Awad, Hossam Ebaid, Abdelaziz S. A. Abuelsaad
Abstract
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.