Gold Shell-Isolated Nanoparticles Differentially Affect Neutrophil Antimicrobial Function

Gold-based nanomaterials are widely explored for biomedical applications, yet their interactions with innate immune cells remain insufficiently defined. Herein, we evaluated the interaction of gold shell-isolated nanoparticles (AuSHINs) with freshly isolated human neutrophils, integrating physicochemical characterization with uptake, viability, and functional assays. AuSHINs were readily internalized within 5 min, and cell-death profiling showed no increase in necrosis across the tested range, whereas apoptotic signaling became evident from 32 μg/mL and was more pronounced at higher exposures. At lower doses (6.4-32 μg/mL), viability was maintained, and neutrophil effector outputs shifted: AuSHINs acted as chemotactic cues in Boyden chamber assays, reduced neutrophil-mediated bacterial clearance and promoted NET formation to levels comparable to PMA. At higher concentrations, NET release decreased in parallel with reduced viability. By mapping these responses across concentration windows, this work frames how gold-silica nanostructures can redirect neutrophil antimicrobial strategies and highlights the need to evaluate immune function alongside standard cytotoxicity end points when designing and benchmarking nanomaterials intended for biological environments.