Abstract
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.
Highlights
Synthetic amorphous silica (SAS) nanoparticles (NPs) are produced in large amounts for applications in industry and medicine
It is tempting to speculate that microlesions in the gut epithelium due to cell death could contribute to the inflammatory symptoms
There is a constant renewal of epithelial cells, which originate from stem cells and progressively differentiate to become mature enterocytes
Summary
Synthetic amorphous silica (SAS) nanoparticles (NPs) are produced in large amounts for applications in industry and medicine. Many consumer products including food contain SAS, which occurs in different forms depending on the process of its manufacture. Food-grade SAS (E551) includes fumed (pyrogenic) silica and hydrated silica (precipitated silica, silica gel, and hydrous silica). Colloidal silica (silica sol) is not authorized as a food additive [1], but is an emerging material for various biomedical applications such as drug delivery [2]. Addition of SAS to food products has, for example, stabilizing, anti-caking, anti-settling, and emulsifying effects [3]. SAS food additive has been used for decades and is considered to be safe for consumers. Yang et al [4] reported the occurrence of SAS at 1.3–16.3 mg Si/g dry food product, mainly in processed food such as coffee creamer, pudding powder, cake mix, or in probiotic tablets. In all exposure scenarios studied by EFSA (European Food Safety Authority), the lowest exposure was reported in the elderly, while the highest was in infants and in children, ranging from 3.9 to 74.2 mg/kg body weight per day and from 8.4 to 162.7 mg/kg body weight per day, respectively [1]
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