Plant�Inspired Gold Nanoparticles (AuNPs)�Based Nanomedicine and Molecular Imaging for Breast Cancer Drug Delivery

Breast cancer is the most commonly diagnosed malignancy among women worldwide, with treatment often challenged by genetic and non-genetic resistance mechanisms. This study presents a novel, eco-friendly approach for synthesizing gold nanoparticles (AuNPs) using the ethyl acetate extract of Piper betle var. Mysuru, an agriculturally significant plant known for its bioactive phytochemicals. This green synthesis method not only minimizes environmental impact but also enhances the therapeutic potential of the resulting nanoparticles. Characterization of the AuNPs revealed their spherical, nanocrystalline nature with a face-centered cubic lattice and diameters ranging from 14 to 34 nm (25 nm average). The AuNPs demonstrated remarkable cytotoxicity against MCF-7 breast cancer cell lines, achieving an IC50 value of 9.06 ± 0.51 μg/mL, outperforming plant extracts and conventional therapies. Hemolytic assays further confirmed their safety, with minimal hemolysis (8.67%), supporting their potential for safe systemic circulation. The study's novelty is identifying decoside, a bioactive compound in P. betle, as a potent inhibitor of the EGFR signaling pathway. Molecular docking and dynamic simulations revealed strong binding interactions between decoside and target proteins, disrupting pathways critical to cancer cell proliferation. This work highlights the potential of P. betle-mediated AuNPs as a sustainable, scalable, and highly effective solution for breast cancer therapy. Their affordability, eco-friendliness, and enhanced therapeutic efficacy underscore their promise for clinical applications and large-scale production, paving the way for advanced cancer therapeutics with reduced side effects. © 2025 John Wiley & Sons Ltd.