Dual Antibacterial and Anticancer Functionality of Self-Assembled Dipeptide-Capped Silver Nanoparticles: Molecular Insights into Protein–Nanoparticle Interactions

The nanobased drug delivery system has become a responsive and potential therapeutic approach for the therapeutic implication against multidrug-resistant bacterial infections and malignant cells with a convenient synthesis process, customization, and site-specific active targeting. In this study, self-assembled peptide-functionalized silver nanoparticles (SAP@AgNPs) were fabricated via a bottom-up approach using NaBH₄ as a reducing agent. The physicochemical properties of the synthesized SAP@AgNPs were observed by various standard characterization techniques, like UV-vis, FTIR, XPS, TEM, FE-SEM, DLS, ZETA, and XRD, which reveal a self-assembled nanostructure having a dipeptide on its surface. SAP@AgNPs showed dose-dependent antibacterial efficacy against clinically isolated multidrug-resistant <i>Staphylococcus aureus</i> and <i>Escherichia coli</i> bacterial strains. Notably, SAP@AgNPs demonstrated superior antibacterial activity against <i>E. coli</i> (MBC: 0.04 nM) compared to <i>S. aureus</i> (MBC: 0.05 nM). The synthesized SAP@AgNPs were further evaluated for their anticancer potency against leukemic cells (K-562), where the IC₅₀ was found to be 0.029 nM concentration of the functionalized nanoparticles. Elevated levels of oxidative stress formation because of considerable ROS generation following treatment with SAP@AgNPs may lead to effective antibacterial and anticancer activity. The SAP@AgNPs demonstrated negligible hemolysis (≤2%) at concentrations up to 0.04 nM. In contrast, the IC₅₀ values for SAP@AgNPs against HEK-293 and PBMCs were determined to be 0.035 and 0.155 nM, respectively, suggesting the particles' biocompatibility. Furthermore, it was established by various <i>in silico</i> approaches that SAP@AgNPs potently interacted with distinct cell surface proteins of the tested bacterial strains as well as cancer cells. Furthermore, multiple <i>in silico</i> techniques revealed that SAP@AgNPs strongly interacted with distinct cell surface proteins of the investigated bacterial strains as well as cancer cells, which could be the key component in the entire study's high biological effectiveness.