Light-Responsive Ag ₄₄ –Templated Silver Nanoparticles for Targeted Antibacterial Therapy: Harnessing Size-Dependent Synergistic Action Mechanisms

Silver nanoparticles (Ag NPs) have garnered significant attention in biomedical and optoelectronic applications due to their localized surface plasmon resonance and antimicrobial properties. However, the aqueous-phase synthesis of structurally homogeneous Ag NPs with precise dimensional control remains challenging, particularly for achieving scalable antibacterial efficacy. Herein, we report a green strategy using atomically precise Ag₄₄ nanoclusters as nucleation templates to produce monodisperse Ag NPs (3-250 nm) with narrow polydispersity (<3% deviation) and tunable surface charge (-39 to -56 mV). Systematic evaluation revealed a strong inverse size-efficacy correlation (3-50 nm range), where <i>Staphylococcus aureus</i> (G⁺) exhibited heightened sensitivity. These NPs further demonstrated size-dependent antibacterial activity against both <i>S. aureus</i> and <i>E. coli</i>. Mechanistic studies indicate that enhanced surface oxidation states in smaller NPs facilitate bacterial membrane disruption. Crucially, blue light irradiation (450 nm, 0.3 mW/cm²) synergistically enhanced antibacterial efficacy >10-fold, reducing MIC values to 2 μg/mL through: (i) Ag⁺ release from the Ag₄₄@Ag core-shell structure; (ii) plasmon-mediated ROS generation; and (iii) photoenhanced surface reactivity. This multimechanistic antibacterial platform outperforms conventional Ag NPs, while the template-guided synthesis offers a sustainable paradigm for precision nanomaterials with tailored functionalities in photonic medicine and nanoelectronics.