Several in vitro studies have suggested that
silica nanoparticles (NPs) might induce adverse effects in gut cells. Here, we used the human
colon cancer epithelial cell line HCT116 to study the potential cytotoxic effects of ingested
silica NPs in the presence or absence of serum. Furthermore, we evaluated different physico-chemical parameters important for the assessment of nanoparticle safety, including primary particle size (12, 70, 200, and 500 nm) and surface modification (-NH2 and -COOH).
Silica NPs triggered cytotoxicity, as evidenced by reduced metabolism and enhanced membrane leakage. Automated microscopy revealed that the
silica NPs promoted apoptosis and
necrosis proportional to the administered specific surface area dose. Cytotoxicity of
silica NPs was suppressed by increasing amount of serum and surface modification. Furthermore, inhibition of
caspases partially prevented
silica NP-induced cytotoxicity. In order to investigate the role of specific cell death pathways in more detail, we used isogenic derivatives of HCT116 cells which lack the
pro-apoptotic proteins p53 or BAX. In contrast to the anticancer drug
cisplatin,
silica NPs induced cell death independent of the p53-BAX axis. In conclusion,
silica NPs initiated cell death in
colon cancer cells dependent on the specific surface area and presence of serum. Further studies in vivo are warranted to address potential cytotoxic actions in the gut epithelium. The unintended toxicity of
silica NPs as observed here could also be beneficial. As loss of p53 in
colon cancer cells contributes to resistance against anticancer drugs, and thus to reoccurrence of
colon cancer, targeted delivery of
silica NPs could be envisioned to also deplete p53 deficient
tumor cells.