Amorphous nanosilica induce endocytosis-dependent ROS generation and DNA damage in human keratinocytes

TLDR

Clarifying the physicochemical properties of nanomaterials and the endocytosis pathway of amorphous nanosilica is crucial for hazard assessment and designing safer forms. The study examined how particle size of amorphous nanosilica influences its in vitro effects on human keratinocytes. The authors assessed the size‑dependent biological effects of nSP on HaCaT cells in vitro. Exposure to 70‑nm amorphous nanosilica markedly increased ROS production and DNA damage in HaCaT cells, whereas 300‑ and 1000‑nm particles elicited a much weaker response, and inhibition of endocytosis with cytochalasin D attenuated these effects, demonstrating that particle size governs silica‑induced oxidative stress and genotoxicity.

Abstract

Abstract Background Clarifying the physicochemical properties of nanomaterials is crucial for hazard assessment and the safe application of these substances. With this in mind, we analyzed the relationship between particle size and the in vitro effect of amorphous nanosilica (nSP). Specifically, we evaluated the relationship between particle size of nSP and the in vitro biological effects using human keratinocyte cells (HaCaT). Results Our results indicate that exposure to nSP of 70 nm diameter (nSP70) induced an elevated level of reactive oxygen species (ROS), leading to DNA damage. A markedly reduced response was observed using submicron-sized silica particles of 300 and 1000 nm diameter. In addition, cytochalasin D-treatment reduced nSP70-mediated ROS generation and DNA damage, suggesting that endocytosis is involved in nSP70-mediated cellular effects. Conclusions Thus, particle size affects amorphous silica-induced ROS generation and DNA damage of HaCaT cells. We believe clarification of the endocytosis pathway of nSP will provide useful information for hazard assessment as well as the design of safer forms of nSPs.