Nanoforms of mesoporous silica (mSiNPs) are increasingly applied in medicine, imaging, energy storage, catalysis, biosensors, and bioremediation. The impact of their physicochemical properties on health and the environment remain to be elucidated. In this work, newly synthesized mesoporous silica (sizes: 25, 70, 100, 170, and 600 nm; surface functionalization: pristine, C3-, and C11-COOH moieties) were assessed for cytotoxicity and induction of inflammatory responses in vitro (A549, THP-1, J774A.1 cells). All toxicity end points were integrated to obtain simple descriptors of biological potencies of these mSiNPs. The findings indicate that mSiNPs are less bioactive than the nonporous reference SiNP used in this study. The C3-COOH-modified mSiNPs were generally less cytotoxic than their pristine and C11-modified counterparts in the nanorange (≤100 nm). Carboxyl-modified mSiNPs affected inflammatory marker release across all sizes with cell-type specificity, suggesting a potential for immunomodulatory effects. Surface area, size, extent of agglomeration, ζ-potential, and surface modification appeared to be important determinants of cytotoxicity of mSiNPs based on association tests. Pathway analysis identified particle and cell-type-specific alteration of cellular pathways and functions by mSiNPs. The integration of exposure-related biological responses of multiple cell lines to mSiNPs allowed for a comprehensive evaluation of the impact of physicochemical factors on their toxicity characteristics. The integrated multilevel toxicity assessment approach can be valuable as a hazard screening tool for safety evaluations of emerging nanomaterials for regulatory purpose.
Keywords: cytokines; cytotoxicity; mesoporous silica nanoparticles; pathway analysis; size; surface modification.