Biogenic Silver-Selenium nanocomposite with anticancer activity and potent efficacy against vancomycin-resistant Staphylococcus aureus.

The rapid emergence of multi-drug resistant (MDR) pathogenic bacteria as well as the continued burden of malignant diseases requires the safe development of novel and multifunctional therapeutic agents. The WHO designated vancomycin-resistant Staphylococcus aureus (VRSA) as "high priority" AMR pathogen. Thus, this study aimed to ecofriendly synthesis of silver-selenium nanocomposite (Ag-Se NC) and evaluate its in vitro anticancer effect and inhibitory activity against VRSA clinical isolates. Biogenic Ag-Se NC was successfully synthesized using the aqueous peel extract of Cucumis melo (C. melo) through an eco-friendly green synthesis approach. Following visual color transformation of the preparation mixture, nanocomposite formation was validated based on comprehensive physicochemical characterization using different spectroscopic analyses. The greenly synthesized Ag-Se NC revealed the Ag and Se specific surface plasmon resonance (SPR) peaks, high crystallinity, and predominantly spherical morphology with an average particle size of ~35 nm. Biological evaluations revealed that Ag-Se NC possesses selective cytotoxicity, displaying low toxicity toward WI-38 normal lung fibroblasts (IC₅₀ = 203.4 µg/mL) while exerting a potent, concentration-reliant inhibitory effect towards malignant cell lines, including hepatocellular carcinoma (Hep-G2) and breast adenocarcinoma (MCF-7) with IC50 90.97 and 38.18 μg/mL respectively. Furthermore, the Ag-Se NC demonstrated appreciated antibacterial activity, in comparison with the linezolid standard antimicrobial agent, against 11 VRSA clinical isolates, with MIC values ranging from 64 to 512 µg/mL and a mean MIC of 203.64 µg/mL. The marked NC bactericidal effects were indicated by their minimum inhibitory concentration index (MICi) values of 1-4, rapid time-kill kinetics, and significant membrane disruption evidenced by the protein leakage assay. The obtained NC also exhibited a respected inhibitory effect against VRSA biofilm development, in the range of 34.68 ± 2.4-72.89 ± 1.87%, as well as a strain-dependent partial eradication effect on the fully formed bacterial biofilm, ranging from 16.81 ± 0.96 to 42.59 ± 0.78%. Notably, variable interactions were observed when Ag-Se NC was combined with vancomycin against VRSA isolates; one isolate showed synergistic interaction with fractional inhibitory concentration index (FICi) = 0.5 and three isolates exhibited additive effects (FICi ranged from 0.5 to 1). In conclusion, these findings highlight Ag-Se NC as a promising green-synthesized nanoplatform with combined anticancer and bacterial inhibitory effects in both planktonic and biofilm growth forms and antimicrobial-potentiating activities.