Physicochemical Properties Can Be Key Determinants of Mesoporous Silica Nanoparticle Potency <i>in Vitro</i>

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

Differential cytotoxic and inflammatory potency of amorphous silicon dioxide nanoparticles of similar size in multiple cell lines

<p>The likelihood of environmental and health impacts of silicon dioxide nanoparticles (SiNPs) has risen, due to their increased use in products and applications. The biological potency of a set of similarly-sized amorphous SiNPs was investigated in a variety of cells to examine the influence of physico-chemical and biological factors on their toxicity. Cellular LDH and ATP, BrdU incorporation, resazurin reduction and cytokine release were measured in human epithelial A549, human THP-1 and mouse J774A.1 macrophage cells exposed for 24 h to suspensions of 5–15, 10–20 and 12 nm SiNPs and reference particles. The SiNPs were characterized in dry state and in suspension to determine their physico-chemical properties. The dose-response data were simplified into particle potency estimates to facilitate the comparison of multiple endpoints of biological effects in cells. Mouse macrophages were the most sensitive to SiNP exposures. Cytotoxicity of the individual cell lines was correlated while the cytokine responses differed, supported by cell type-specific differences in inflammation-associated pathways. SiNP (12 nm), the most cytotoxic and inflammogenic nanoparticle had the highest surface acidity, dry-state agglomerate size, the lowest trace metal and organics content, the smallest surface area and agglomerate size in suspension. Particle surface acidity appeared to be the most significant determinant of the overall biological activity of this set of nanoparticles. Combined with the nanoparticle characterization, integration of the biological potency estimates enabled a comprehensive determination of the cellular reactivity of the SiNPs. The approach shows promise as a useful tool for first-tier screening of SiNP toxicity.</p