Influence of size, surface area and microporosity on the in vitro cytotoxic activity of amorphous silica nanoparticles in different cell types

Abstract

Identifying the physico-chemical characteristics of nanoparticles (NPs) that drive their toxic activity is the key to conducting hazard assessment and guiding the design of safer nanomaterials. Here we used a set of 17 stable suspensions of monodisperse amorphous silica nanoparticles (SNPs) with selected variations in size (diameter, 2–335 nm), surface area (BET, 16–422 m²/g) and microporosity (micropore volume, 0–71 μl/g) to assess with multiple regression analysis the physico-chemical determinants of the cytotoxic activity in four different cell types (J774 macrophages, EAHY926 endothelial cells, 3T3 fibroblasts and human erythrocytes). We found that the response to these SNPs is governed by different physico-chemical parameters which vary with cell type: In J774 macrophages, the cytotoxic activity (WST1 assay) increased with external surface area (αs method) and decreased with micropore volume (r² of the model, 0.797); in EAHY926 and 3T3 cells, the cytotoxic activity of the SNPs (MTT and WST1 assay, respectively) increased with surface roughness and small diameter (r², 0.740 and 0.872, respectively); in erythrocytes, the hemolytic activity increased with the diameter of the SNP (r², 0.860). We conclude that it is possible to predict with good accuracy the in vitro cytotoxic potential of SNPs on the basis of their physico-chemical characteristics. These determinants are, however, complex and vary with cell type, reflecting the pleiotropic interactions of nanoparticles with biological systems.

Keywords::

• Nano-surfaces
• nanoparticles
• nanotoxicology
• particle toxicology

Acknowledgments

The excellent technical assistance of Francine Uwambayinema and the competent statistical advice of Mathieu Roelants were greatly appreciated.

Declaration of interest: This work was financed by the Belgian Science Policy Ministry (contract SD/HE/02A). JAM and CEAK acknowledge support by the Flemish Government via long term structural funding (Methusalem). The authors would like to report no conflict of interests. The authors are entirely responsible for the content and writing of the manuscript.