Influence of Physicochemical Characteristics and Stability of Gold and Silver Nanoparticles on Biological Effects and Translocation across an Intestinal Barrier-A Case Study from In Vitro to In Silico.

Yvonne Kohl,Stephan Dähnhardt-Pfeiffer,Florian Meier,Sylvia Wagner,Thorsten Lehr,Lukas Kovar,Dominik Selzer,Roland Drexel,Michelle Hesler,Hagen Von Briesen

doi:10.3390/nano11061358

Abstract

A better understanding of their interaction with cell-based tissue is a fundamental prerequisite towards the safe production and application of engineered nanomaterials. Quantitative experimental data on the correlation between physicochemical characteristics and the interaction and transport of engineered nanomaterials across biological barriers, in particular, is still scarce, thus hampering the development of effective predictive non-testing strategies. Against this background, the presented study investigated the translocation of gold and silver nanoparticles across the gastrointestinal barrier along with related biological effects using an in vitro 3D-triple co-culture cell model. Standardized in vitro assays and quantitative polymerase chain reaction showed no significant influence of the applied nanoparticles on both cell viability and generation of reactive oxygen species. Transmission electron microscopy indicated an intact cell barrier during the translocation study. Single particle ICP-MS revealed a time-dependent increase of translocated nanoparticles independent of their size, shape, surface charge, and stability in cell culture medium. This quantitative data provided the experimental basis for the successful mathematical description of the nanoparticle transport kinetics using a non-linear mixed effects modeling approach. The results of this study may serve as a basis for the development of predictive tools for improved risk assessment of engineered nanomaterials in the future.

Highlights

IntroductionWhen manufacturing new products that contain engineered nanomaterials (ENM), often referred to as nano-enabled products [1], in addition to improving product functionality and quality, the safety of the products for the user as well as safe manufacturing (safety of workers) must be ensured
SbD is not a new concept; it has already been applied by other industries, among others in the pharmaceutical sector to ensure safety throughout the drug discovery and development process [4,6,7,8]
This study focuses on the influence of the physicochemical characteristics and the stability of metallic nanoparticles, in particular gold nanoparticles (AuNP) and silver nanoparticles (AgNP) of different sizes, shapes and surface zeta potentials, on the translocation through the gastrointestinal (GI) barrier, along with their associated biological effects, such as membrane damage, inflammation, apoptosis or genotoxicity

Summary

Introduction

When manufacturing new products that contain engineered nanomaterials (ENM), often referred to as nano-enabled products [1], in addition to improving product functionality and quality, the safety of the products for the user as well as safe manufacturing (safety of workers) must be ensured. SbD is not a new concept; it has already been applied by other industries, among others in the pharmaceutical sector to ensure safety throughout the drug discovery and development process [4,6,7,8]. Its implementation in nanotechnology remains challenging and requires a comprehensive and well-founded database for functionality, toxicity and exposure of ENM.

Methods

Results

Conclusion