NANOaers – Fate of aerosolized nanoparticles: the influence of surface active substances on lung deposition and respiratory effects
The use of manufactured nanomaterials (MNM) in particulate form is increasing steadily, but little is known about their fate and effects after release into the airborne state and subsequent deposition in the respiratory tract. Especially the influence of matrix effects in liquid formulations on the fate of nanomaterials, e.g. their ability to absorb other substances and serving as a carrier to otherwise inaccessible sites in the lungs of organisms still remains to be investigated. These aspects are necessary as humans and the environment are hardly exposed to manufactured nanomaterials that are not altered by any chemical substances, either coming from the products they are used in or by reactions in the atmosphere. Thus, for the first time, the ERA-Net SIINN project NANOaers addresses the open question regarding the influence of aerosolisation and of chemical surface-active substances on the fate of nanomaterials and their potential subsequent uptake by airway epithelium and effects. The project combines physicochemical and toxicological in vitro-3D cell models, precision cut lung slices (PCLS) and in vivo experiments.
This approach is being designed to describe exemplarily the different fates of two representative classes of manufactured nanomaterials relevant for inhalation exposure. To specify the nano-effect, all experiments and investigations will additionally be conducted with micro-sized particles.
- soluble particles with a substance-specific toxicity using the example of silver nanoparticles (Nano-Ag)
- granular biodurable particles (GBP) using the example of cerium dioxide nanoparticles (Nano-CeO2)
An experiment will be established which will enable the release of manufactured nanomaterials from liquid matrices into the airborne state and which allows for a controlled variation of parameters influencing aerosol formation. The fate of manufactured nanomaterials will then be investigated after deposition on airway epithelia and abiotic surfaces. The aging process in the aerosol may change the morphology, density, size range and distribution of the particles. This aging process is assumed to be affected by physicochemical properties of the manufactured nanomaterials, interaction with substances like auxiliary substances and the releasing process parameters.
Furthermore, in vitro and in vivo toxicity tests using respiratory cell types to test toxicological endpoints after deposition of manufactured nanomaterials on airway epithelia are conducted. These endpoints include cytotoxicity, pro-inflammatory cytokine expression, haemolytic capacity and lung clearance over time as well as extra-pulmonary retention, the elimination kinetics and the analysis of intracellular dose.
The work plan is completed with the development of an experimentally based model for predicting the fate of manufactured nanomaterials during spraying and aerosol transport.
The framework of the work plan is provided by three administrative work packages dealing with the coordination of the project, as well as with the dissemination of the results and with the harmonisation. The latter work package is focusing on the comparison of different analytical techniques as well as toxicity assays fostering the harmonisation between laboratories, especially on a transcontinental level.
Project Website: www.nanoaers.eu/index.html
Grant Number: ERA-Net SIINN - FKZ 03XP0064
Duration: 01.05.2016 - 30.09.2019 (extended to 31.10.2019)