We report different mesoporosity-dependent and functional group-dependent cytotoxicity and endocytosis of various silica nanomaterials on suspended and adherent cells. This dependency further varied with incubation time and particle dosage, and appeared to be associated with the particles’ endocytotic efficiency and their chemical and physical properties. We studied two common mesoporous nanomaterials (MSNs), MCM-41 and SBA-15, and one type of solid-cored silica microsphere, paralleled by their quaternary amine functionalized counterparts. Compared to SBA-15, MCM-41 has a larger surface area but smaller pore size, whereas SMS exhibits low surface area and poor porosity. In Jurkat cells, SBA-15 and MCM- 41 exhibited different cytotoxicity profiles. However, no significant cell death was detected when treated with the aminated MSNs, indicating that the positively charged quaternary amines prevented cellular injury from mesoporous nanoparticles. Furthermore, the effective internalization of MSN but not aminated- MSNs was clearly observed, in line with their consequent cytotoxicity. SK-N-SH (human neuroblastoma) cells were found to be more resistant to the treatment of MSN, whether aminated or not. Incubation with either SBA-15 or MCM-41 over time showed a recovery in cell viability, while exposure to MSN-N particles did not induce a noticeable cell death until longer incubation with high dosage of 200 μg/mL was applied. Both aminated and nonaminated silica spheres exhibited instant and constant toxicity on Jurkat (human T-cell lymphoma) cells. TEM images revealed successful endocytosis of SMS and SMSN, although SMS-N appeared to accumulate more in the nucleus. For SK-N-SH cells, low dosage of SMS was found to be less toxic, whereas high dosage produced profound cell death
