Engineering silver domains in mesoporous silica nanostructures for enhanced antibacterial activity

The incidence of antibiotic resistance has urgently requested for effective antibacterial agents. Silver nanoparticles (Ag NPs) demonstrated excellent antibacterial properties, effectively targeting and eliminating various bacterial strains through multiple mechanisms. However, their effectiveness is often limited by aggregation and rapid oxidation, especially in the case of smaller NPs, which would significantly reduce their biocidal activity. Anchoring Ag NPs on inorganic carriers can overcome this limitation improving both stability and long-term antibacterial efficiency. In this study, sub-micrometer mesoporous silica nanoparticles (MSNs), with large specific surface area and surface amino groups are used to template the in-situ synthesis of Ag domains. To investigate how size, loading and spatial distribution within the mesoporous framework of these Ag domains affect antibacterial activity, three distinct types of MSN-Ag nanocomposites are here synthesized and thoroughly characterized by spectroscopic, morphological and textural analyses. Their antibacterial activity is evaluated against Escherichia coli ( E. coli ), a high priority antibiotic-resistant pathogen. Using tetrakis(hydroxymethyl)phosphonium chloride as reducing agent for silver precursor, at different concentration in aqueous medium, two MSN-Ag samples are produced: one with ultrasmall Ag domains (< 2 nm in diameter, MSN-Ag THPC 1) and another with larger Ag domains (∼ 23 nm (MSN-Ag THPC 2), both distributed within the mesoporous structures. Conversely, 6 nm sized Ag domains located at the MSN surface can be achieved using butyl amine as reducing and stabilizing agent. All MSN-Ag nanocomposites demonstrate significantly enhanced antibacterial activity at low doses (1 μg/mL) compared to free Ag NPs. Notably, MSN-Ag BuA shows the highest antibacterial efficacy, achieving 49 % inhibition of E. coli cell growth after 180 min and high Ag + release percentage (14 %). This superior performance is attributed to optimal Ag domain size, to their localization at the surface of the MSN-NH 2 and to the nucleophilic nature of butylamine, which may promote the formation of water-soluble Ag + complexes , enabling rapid and sustained ions release. These findings highlight that, beyond a mitigated aggregation, the size and surface characteristics of the Ag domains in MSN-based nanocomposites play a crucial role in determining their antibacterial effectiveness.