Plant-Derived Silver Nanoparticles For Sirna-Mediated Suppression of EGFR Expression in Non-Small Cell Lung Cancer

Abstract

Non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer and remains a major cause of cancer-related mortality worldwide. The epidermal growth factor receptor (EGFR) plays a critical role in NSCLC progression by regulating cellular proliferation, survival, migration, and invasion, making it an attractive therapeutic target. In the present study, plant-derived silver nanoparticles (AgNPs) were developed as a green nanotechnology-based platform for the delivery of EGFR-targeting small interfering RNA (siRNA) to enhance gene-silencing efficiency and anticancer activity. Silver nanoparticles were synthesized using Moringa oleifera leaf extract and characterized using UV–Visible spectroscopy, dynamic light scattering (DLS), zeta potential analysis, Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). The synthesized nanoparticles exhibited favorable physicochemical properties, including nanoscale size distribution, good colloidal stability, and suitable surface characteristics for siRNA loading. EGFR-siRNA was successfully conjugated to the AgNPs with high loading efficiency and enhanced protection against nuclease-mediated degradation. Cellular uptake studies demonstrated significantly improved internalization of AgNP-siRNA nanocomplexes compared with free siRNA. Quantitative RT-PCR and Western blot analyses confirmed substantial suppression of EGFR mRNA and protein expression in NSCLC cells. Furthermore, treatment with AgNP-siRNA nanocomplexes significantly reduced cell viability and proliferation, induced cell cycle arrest and apoptosis, and inhibited cellular migration and invasion. These findings demonstrate that plant-derived AgNPs provide an effective and environmentally sustainable delivery system for EGFR-targeted siRNA therapy. The developed nanoplatform offers promising potential for precision nanomedicine and targeted treatment of NSCLC.