Macrophage Responses to Silica Nanoparticles: Role of Physicochemical Properties and Surface Modification

Silica nanoparticles are widely studied nanomaterials for biomedical applications owing to their tunable physicochemical properties, such as size, porosity, geometry, and surface modification. Despite their promising potential, concerns regarding their safety continue to limit clinical translation. In this study, we systematically investigated how key physicochemical parameters and surface attachment of poly(ethylene glycol) (PEG) affect the cytotoxicity and immune activation profiles of silica nanoparticles in macrophages. A structurally diverse set of silica nanoparticles (rod, spherical, porous, nonporous, and surface-modified) was synthesized and characterized. RAW 264.7 macrophages were used as a model cell line to evaluate nanoparticle internalization, membrane integrity, apoptosis, cell cycle progression, and macrophage activation. While PEGylation and physicochemical variations significantly influenced both cellular uptake and maximum nontoxic dose, none of the tested nanoparticles impaired macrophage viability or baseline functionality at their respective saturation points. Notably, PEGylated silica nanoparticles approximately 100 nm in diameter and rod-shaped nanoparticles elicited pronounced immune activation, highlighting their distinct immunomodulatory potential despite the preserved cellular integrity.