Polymer-stabilized amorphous CuO-ZnO hybrid nanocomplex as a promising candidate for antimicrobial therapy and controlled drug delivery with molecular docking insights.

In this study, multifunctional polymer-stabilized CuO-ZnO hybrid nanocomplexes were developed through a green synthesis approach and systematically evaluated for their antimicrobial and protein delivery potential. Bimetallic CuO-ZnO nanoparticles were biosynthesized using extracts of Cotoneaster horizontalis, Salvia officinalis, and Laurus nobilis, followed by integration into chitosan/nanochitosan-P(MMA-co-MAA) copolymer matrices. The resulting nanocomplexes were characterized using SEM, DLS, FT-IR, and XRD analyses, confirming successful nanoparticle formation, homogeneous dispersion, and predominantly amorphous structures, with particle sizes ranging from 62 to 138 nm. Among the formulations, nanochitosan-based systems exhibited improved structural compactness and reduced polydispersity. Molecular docking simulations revealed strong and stable interactions between the Cu-Zn alloy-modified polymeric carriers and bovine serum albumin, as well as remarkably high binding affinities toward key bacterial and fungal virulence proteins, including Sortase A, TolC, and CYP51. These findings suggested enhanced multivalent interaction capabilities of the nanocomplexes. In vitro antimicrobial assays corroborated the computational predictions, demonstrating pronounced antibacterial and antifungal activities (15-22 mm against E. coli, 17-24 mm against S. aureus and 21-25 mm against A. niger) with low minimum inhibitory concentrations (0.50 mg/mL for E. coli and 0.25 mg/mL for S. aureus). Furthermore, in vitro release studies using bovine serum albumin and human insulin as model biomolecules revealed sustained and controlled release profiles over seven days, with minimal burst effects. Nanochitosan-based systems exhibited slightly slower release kinetics, attributed to denser polymeric networks and stronger biomolecule-carrier interactions. The incorporation of P(MMA-co-MAA) further contributed to pH-responsive and diffusion-controlled release behavior. Collectively, this study presents an integrated experimental and computational strategy for designing biocompatible, green-synthesized CuO-ZnO nanocomplexes with dual antimicrobial and drug delivery functionalities. The developed platform may hold strong potential for biomedical applications, including drug delivery systems, wound dressings, and implant-associated infection control.