Engineering Mesoporous Silica Hosts for Ultrasmall ZnO Nanoparticles: A Dendritic Polymer-Assisted Strategy Towards Sustainable, Safe, and Effective Antibacterial Systems

In response to the urgent need for sustainable antibacterial solutions against antibiotic-resistant pathogens, this study presents a facile dendritic polymer-assisted approach for synthesizing highly active ZnO/mesoporous silica nanocomposites (SBA-15, SBA-16, KIT-6, MSU-X). Two hyperbranched polymers-polyethyleneimine (PEI) and carboxy-methylated polyethyleneimine (Trilon-P, TrP)-were employed as templating and metal-trapping agents. The influence of pore geometry, polymer functionality, and polymer-loading method (wet or dry impregnation) on ZnO nanoparticle (NP) formation was systematically examined. All nanocomposites exhibited high structural homogeneity, incorporating ultrasmall or amorphous ZnO NPs (1-10 nm) even at 8 wt.% Zn loading. Zn uptake was strongly dependent on polymer end groups, while the spatial distribution of ZnO NPs was dictated by the silica host structure. Antibacterial assays against <i>Staphylococcus aureus</i> revealed remarkable activity, particularly for ZnO/SBA-15_PEI, ZnO/SBA-16_PEI, and ZnO/MSU-X_TrP nanocomposites, with minimum inhibitory concentrations of 1-2.5 μg mL^-1 Zn and over 90% mammalian cell viability. Life Cycle Assessment identified energy use as the main environmental factor, with ZnO/SBA-15_PEI_WI displaying the lowest impact. Overall, the interplay between silica pore architecture, polymer type, and impregnation method governs ZnO accessibility and bioactivity, establishing a versatile strategy for designing next-generation ZnO/SiO₂ nanocomposites with tunable antibacterial efficacy and minimal cytotoxic and environmental footprint.