Physics helps to predict nanomaterials toxicity
|On a daily basis, people are exposed to a multitude of hazardous airborne dust matter, of mostly industrial origin, with notable deposition in lungs. Hence, there is a need for identification and prediction of nanomaterial‐associated diseases, currently hindered due to the lack of in‐depth understanding of causal relationships between material properties and acute exposures or chronic adverse conditions. This need has been addressed by the European Commission via a project on development of predictive methods for nanomaterial toxicity that was led by UCD researchers. EU Horizon 2020 project SmartNanoTox (2016-2020) was coordinated by Vladimir Lobaskin, UCD School of Physics and included SBI team Boris Kholodenko, Vadim Zhernovkov, and David Gomez-Matallanas.|
The SmartNanoTox consortium proposed a new paradigm in the nanomaterial toxicity assessment – a mechanism-aware testing, based on tracking of all the significant interactions between the material and biological molecules and tissues from the initial contact to the adverse outcome. This programme requires researchers to follow the nanoparticles inside live tissues, quantify the bio-nano interactions, and trace the organism’s responses at all scales. Although the goal looks very ambitious, it was argued that such an approach is necessary to identify the material’s properties of concern, and allow to change of avoid those at the stage of product development. A specific focus of the project was on inhalation exposure and pulmonary diseases that may be caused by common industrial nanopowders.
A recent publication in Advanced Materials journal, co-authored by UCD researchers, illustrates this novel approach in action. Inhaled nanoparticles are tracked inside the lung and in contact with vital biomolecules. Using high resolution imaging, gene expression and pathway the team has identified of a vicious cycle of nanomaterials uptake, excretion and quarantining by different cell types in the lung can result in chronic lung inflammation.
The paper is outstanding in many aspects. It accumulates a tremendous research effort invested by the project team over four years. The interdisciplinary team includes biologists, toxicologists, chemists, physicists, materials scientists form 8 labs across Europe, China and Canada. The associated in vivo, in vitro and in silico data are presented in over 180 figures, 42 videos and 12 tables. The team used animal exposure experiments, high-resolution imaging, cell line experiments, systems biology, and computational materials modelling to recover a detailed description of the progression of the disease. Based on the obtained results, in accordance with the SmartNanoTox assessment paradigm, the chronic adverse outcome can be predicted for new nanomaterials without a need for in vivo animal exposure experiment but with only in vitro tests and computational modelling. This demonstration of power of the mechanistic approach to toxicology opens new perspectives in animal-free materials testing and implementation of safety-by-design approach in nanotechnology.
Full article available from Kokot et al, Prediction of Chronic Inflammation for Inhaled Particles: the Impact of Material Cycling and Quarantining in the Lung Epithelium. Adv. Mater. 2020, 2003913.