Bacterial-engineered self-stabilizing ultra-small AgCu nanoparticles for dual antimicrobial-anticancer therapy

Bimetallic silver-copper nanoparticles (AgCu NPs) exhibit enhanced antibacterial properties compared to their monometallic counterparts; however, their clinical translation is limited by poor stability and biocompatibility. Here, we unveil a bacterial incubation-driven synthesis (bacterial-enabled dynamic nanoreactor) of ultra-small AgCu NPs with dual antimicrobial-antitumor functionality. Remarkably, conventional 15 nm AgCu NPs undergo spontaneous size reduction to 2 nm upon interaction with E. coli or S. aureus , accompanied by a complete loss of surface plasmon resonance (SPR) and formation of protein-capped stable dispersions. Mechanistic studies reveal this bacterially triggered transformation involves Ag + release via oxidative dissolution in saline environments, followed by PVP/PVA and bacterial biomolecule-mediated re-nucleation. The US-AgCu NPs demonstrate synergistic therapeutic advantages: Enhanced antibacterial potency compared to parent NPs; pH-selective cytotoxicity; Reusable antimicrobial performance over multiple cycles with minimal resistance development; Long-term stability. This bio-derived strategy achieves kilogram-scale production of therapeutic NPs via continuous fermentation, addressing critical challenges in nanomaterial manufacturing for combating antimicrobial resistance and malignancies. • Bacteria trigger atomic restructuring of AgCu NPs into 2 nm nanoparticles. • PVP/PVA-protein triple shell enables unprecedented colloidal stability. • 23× enhanced antibacterial potency vs parent nanoparticles (MIC 0,067 ppm). • pH-selective cytotoxicity: tumor IC 50 =0.370 μg/mL (B16-F10), normal cell viability >80 %. • Scalable production via continuous fermentation (kg/batch).