Synergistic Antibacterial and Anticancer Effects of a Biohybrid Composed of Zinc Oxide Nanoparticles and <i>Streptococcus Salivarius</i> Bacteriocin

ABSTRACT Antimicrobial therapies are desperately needed since the threat posed by multidrug‐resistant (MDR) bacteria only grows. Bacteriocins produced by Streptococcus salivarius possess promising antibacterial properties, yet their practical application is hindered by low production yield and limited stability. Here, we report the green synthesis of a novel biohybrid by conjugating purified S. salivarius bacteriocins with zinc oxide nanoparticles (ZnONPs), aiming to enhance bacteriocin stability and antimicrobial efficacy. The successful creation of well‐dispersed nanohybrids was validated by thorough characterization using x‐ray diffraction (XRD), transmission electron microscopy (TEM), and scanning electron microscopy (SEM), exhibiting predominantly cubic and spherical morphologies with sizes ranging from 8 to 68 nm. The ZnONPs–bacteriocin nanohybrids demonstrated pronounced antibacterial activity against both Gram‐positive and Gram‐negative MDR pathogens, as evidenced by significant inhibition zones, and low values for the minimum bactericidal concentration (MBC) and minimum inhibitory concentration (MIC). In vitro cytotoxicity, assays revealed a dose‐dependent reduction in the viability of both cancerous (A375) and normal (HdFn) cell lines. The nanohybrid displayed greater cytotoxicity toward A375 cells (IC 50 = 121.7 µg/mL) than HdFn cells (IC 50 = 161.6 µg/mL), indicating a degree of selectivity. Collectively, our results demonstrate that green‐synthesized ZnONPs–bacteriocin biohybrids are eco‐friendly and exhibit potent, broad‐spectrum antimicrobial and selective cytotoxic activities, suggesting their significant potential for biomedical applications targeting resistant bacterial infections and malignant cells.