Polyphenol-Mediated Green Synthesis of TiO2 and ZnO Nanoparticles from Vaccinium corymbosum: Integrating Structural Characterization, Antimicrobial Mechanisms, and Cytocompatibility Assessment

Developing eco-friendly metal oxide nanoparticles (NPs) with plant-based reducing and stabilizing agents offers a sustainable alternative to traditional chemical methods. Nonetheless, the detailed mechanisms by which phytochemicals influence NPs formation, antimicrobial properties, and cytocompatibility remain poorly understood, especially in systems mediated by Vaccinium. This study aimed to synthesize TiO2 NPs and ZnO NPs using Vaccinium corymbosum (blueberry) extract, analyze their structural and surface characteristics, assess their antimicrobial effectiveness and cytotoxicity, and explore potential molecular mechanisms through computational docking. ZnO NPs were produced via alkaline precipitation (pH 12) from ZnCl2, while food-grade TiO2 was mixed with blueberry extract. A comprehensive characterization was carried out using techniques like X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, transmission and scanning electron microscopy (TEM/SEM), dynamic light scattering (DLS), and high-performance liquid chromatography (HPLC) for polyphenol profiling. The antimicrobial activity was tested against Escherichia coli and Salmonella Typhimurium, and the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined. Cytotoxicity was assessed using Gallus gallus domesticus leukocytes and Artemia salina bioassays, and molecular docking simulations were performed to examine polyphenol interactions with the bacterial DNA gyrase subunit B (GyrB). XRD analysis confirmed the presence of wurtzite ZnO (with a crystallite size of 18.2 nm) and anatase TiO2 (12.8 nm after functionalization). HPLC identified key polyphenols, including quercetin, cyanidin, malvidin, and cyanidin-3-glucoside, with patterns indicating stronger adsorption onto TiO2 NPs surfaces. ZnO NPs showed higher antimicrobial effectiveness (>90% inhibition at 2 mg/mL; MIC 0.5–1 mg/mL) compared to TiO2 (72% inhibition at 16 mg/mL; MIC 8–16 mg/mL). Cytotoxicity results indicated concentration-dependent effects. Molecular docking simulations revealed favorable binding energies (−6.2 to −8.4 kcal/mol) for blueberry polyphenols with GyrB, suggesting potential synergistic antimicrobial effects and ROS production. The study highlights a successful green synthesis of bioactive TiO2 NPs and ZnO NPs using Vaccinium corymbosum extract, where polyphenol surface functionalization enhances both colloidal stability and biological activity. This comparative research offers mechanistic insights into how polyphenol-coated NPs work and supports the development of eco-friendly antimicrobial oxide nanomaterials.