Differential Toxicity and Immunomodulatory Effects of Titanium and Silica Nanoparticles in Murine Macrophages

ABSTRACT The integration of nanomaterials into consumer products has outpaced our understanding of their immunological impact. This study evaluates the dose‐dependent effects of two commercial nanoparticle formulations, titanium dioxide (TiO 2 ) and silica (SiO 2 ), on RAW 264.7 murine macrophages. While both formulations possessed primary particle sizes of ∼24–27 nm, they differed in specific surface area, surface chemistry, and baseline aqueous dispersion behavior, with TiO 2 forming larger micron‐scale aggregates. FTIR confirmed characteristic Ti–O–Ti and Si–O–Si structural frameworks. Biological assays revealed contrasting cellular responses. The TiO 2 formulation exhibited substantially lower cytotoxicity than SiO 2 , maintaining viability while stimulating early metabolic activity (up to 130% of control at 24–48 h) and upregulating TNF‐α secretion by 50%–300%. Conversely, SiO 2 induced a potent, dose‐dependent reduction in metabolic activity, reaching an 85% decrease at higher concentrations (250–500 µg/mL) after 72 h. Normalizing nitric oxide secretion to total cellular metabolic activity revealed an activated, hyper‐secretory state in the remaining SiO 2 exposed population, despite reductions in uncorrected TNF‐α levels. These findings demonstrate that the distinct macrophage responses elicited by commercial TiO 2 and SiO 2 formulations are governed by an integrated ensemble of physicochemical properties, including surface area, surface chemical framework, and dispersion dynamics, rather than primary particle size or chemical identity alone.