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

Abstract

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.