Quercetin-loaded Selenium Nanoparticles as a Modulator of Apoptosis, ATG-13, and PDL-1 in Breast Cancer Cell Lines

Breast cancer is the most common cancer among women, but current therapies are limited by toxicity, resistance, and immune evasion. This study developed quercetin-loaded selenium nanoparticles (Que-SeNPs) to improve quercetin stability, bioavailability, and anticancer efficacy. We evaluated their effects on apoptosis, autophagy/PDL-1 axis regulation, and microRNA expression in breast cancer cells. Que-SeNPs were synthesized and characterized by SEM, EDX, DLS, and zeta potential. Entrapment efficiency, drug release, hemolytic activity, and cytotoxicity on normal fibroblasts were assessed. Their impact on BCL-2, caspase-3, ATG-13, PDL-1, and microRNAs (miR-7-5p, miR-146a-3p) was measured by immunofluorescence and qPCR. The nanoparticles were about 115 nm in size, negatively charged (− 30.8 mV), and achieved high entrapment efficiency (96.6%). They reduced hemolysis at high concentrations and showed moderate cytotoxicity to fibroblasts. In breast cancer cells, Que-SeNPs downregulated BCL-2 and PDL-1, upregulated caspase-3 and miR-7-5p, and suppressed ATG-13 and miR-146a-3p. Que-SeNPs showed greater anticancer activity than quercetin alone through apoptosis induction, autophagy/PDL-1 axis regulation in vitro. These findings highlight their promise as a multi-targeted nanotherapy for breast cancer, though in vivo validation is still required.