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 <i>Perilla frutescens</i> 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 <i>Escherichia coli</i> and <i>Staphylococcus aureus</i>, 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 <i>Candida albicans</i> 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.