Stable nanoparticle aggregates/agglomerates of different sizes and the effect of their size on hemolytic cytotoxicity

Abstract

To study the toxicity of nanoparticles under relevant conditions, it is critical to disperse nanoparticles reproducibly in different agglomeration states in aqueous solutions compatible with cell-based assays. Here, we disperse gold, silver, cerium oxide, and positively-charged polystyrene nanoparticles in cell culture media, using the timing between mixing steps to control agglomerate size in otherwise identical media. These protein-stabilized dispersions are generally stable for at least two days, with mean agglomerate sizes of ∼23 nm silver nanoparticles ranging from 43–1400 nm and average relative standard deviations of less than 10%. Mixing rate, timing between mixing steps and nanoparticle concentration are shown to be critical for achieving reproducible dispersions. We characterize the size distributions of agglomerated nanoparticles by further developing dynamic light scattering theory and diffusion limited colloidal aggregation theory. These theories frequently affect the estimated size by a factor of two or more. Finally, we demonstrate the importance of controlling agglomeration by showing that large agglomerates of silver nanoparticles cause significantly less hemolytic toxicity than small agglomerates.

Keywords::

• Nanotoxicity
• silver and gold colloids
• hemolysis
• engineered nanomaterials

Declaration of interest: JMZ was funded by a National Research Council Postdoctoral Fellowship at NIST. MDH was supported in part by the National Science Foundation's Research Experience for Undergraduates (REU) program through the NIST Summer Undergraduate Research Fellowship (SURF) program. The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.