Developing Biocompatible Chitosan-Stabilized Gold Nanoparticles with Anticancer and Antimicrobial Properties: A Computational and Experimental Approach

The present study reports an eco-friendly route for the synthesis of chitosan-stabilized gold nanoparticles (Cs@AuNPs) using Perilla frutescens leaf extract and their dual anticancer and antimicrobial activities. The nanoparticles were comprehensively characterized by ultraviolet–visible (UV–vis) spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and ζ-potential analysis. Cs@AuNPs exhibited a strong surface plasmon resonance peak at 550 nm, face-centered cubic crystallinity with a predominant (111) plane, spherical morphology, particle size ranging from 5–30 nm, and a positive surface charge. Biological assays revealed selective anticancer activity against MCF-7 breast cancer cells with an IC50 of ∼100 μg/mL, while sparing normal MCF-10A cells (>80% viability). Mechanistic studies confirmed significant reactive oxygen species (ROS)-mediated apoptosis, nuclear fragmentation, and regulation of apoptotic proteins. Cs@AuNPs also displayed potent antibacterial activity against Escherichia coli and Staphylococcus aureus, with inhibition zones of up to 15 mm. Computational investigations supported these findings. Molecular docking demonstrated strong binding affinities with the HER2 kinase (−284.3 kcal/mol) and Candida albicans regulator proteins (−343.4 kcal/mol). Molecular dynamics simulations indicated complex stability, while binding free energy calculations (MM/GBSA) with entropy corrections yielded favorable values (−30 to −45 kcal/mol). Density functional theory (DFT) further validated electronic stability, and ADMET profiling predicted high intestinal absorption, nongenotoxicity, and environmental safety. Together, these experimental and computational insights highlight Cs@AuNPs as a biocompatible, sustainable nanoplatform with promising applications in cancer therapy and antimicrobial treatment.