Prediction of Chronic Inflammation for Inhaled Particles: the Impact of Material Cycling and Quarantining in the Lung Epithelium

Abstract

While new exciting applications arise from rapid development of new advanced materials, their lifecycle, from production, processing, to degradation or even combustion, may inevitably result in the release of particulate matter into the environment. [1-3] According to the Organisation for Economic Cooperation and Development (OECD) and the World Health Organization (WHO), inhalation of particulate matter, predominantly of anthropogenic origin, is associated with several million human deaths globally every year. [4-6] While larger particles, deposited in airways, can be efficiently cleared from the bronchial region by the mucociliary escalator, [7] nanomaterials, the term used here for both submicron-sized particles (at least two dimensions below 1 µm) and nanoparticles (at least one dimension below 100 nm), can reach the alveolar region. [7,8] Due to the persistency On a daily basis, people are exposed to a multitude of health-hazardous airborne particulate matter with notable deposition in the fragile alveolar region of the lungs. Hence, there is a great need for identification and prediction of material-associated diseases, currently hindered due to the lack of in-depth understanding of causal relationships, in particular between acute exposures and chronic symptoms. By applying advanced microscopies and omics to in vitro and in vivo systems, together with in silico molecular modeling, it is determined herein that the long-lasting response to a single exposure can originate from the interplay between the newly discovered nanomaterial quarantining and nanomaterial cycling between different lung cell types. This new insight finally allows prediction of the spectrum of lung inflammation associated with materials of interest using only in vitro measurements and in silico modeling, potentially relating outcomes to material properties for a large number of materials, and thus boosting safe-by-design-based material development. Because of its profound implications for animal-free predictive toxicology, this work paves the way to a more efficient and hazard-free introduction of numerous new advanced materials into our lives.

Revealing Inflammatory Indications Induced by Titanium Alloy Wear Debris in Periprosthetic Tissue by Label-Free Correlative High-Resolution Ion, Electron and Optical Microspectroscopy

“…The elevated fluorescence signal could be the first indication of the oxidative stress as a response to pathological conditions or toxic compounds [ 37 ] such as metal wear debris, just recently been found to induce the formation of reactive oxygen species [ 38 ]. Even more, in our latest study, metal oxide nanomaterial has also been found to be one of the key players in chronic inflammation [ 39 ].…”

Controlled Fluorescent Labelling of Metal Oxide Nanoparticles for Artefact-free Live Cell Microscopy

“…In particular, we elucidated the mechanism how certain types of nanomaterials trigger previously unexplained chronic inflammation, based on which we designed an all-in-vitro test for its prediction. [19]…”

“…[11][12][13][14] To unravel fundamental molecular mechanisms of nanoparticle toxicity, it is crucial to identify the molecular events and their causal relationships, which heavily relies on monitoring nanoparticle localization and interaction with living cells in real-time. [15][16][17][18][19] One of the most powerful experimental techniques to study early molecular events including nanoparticle localization and interaction with living cells is fluorescence microscopy, especially its advanced super-resolution implementation with spatial and temporal resolution on the order of tens of nanometers and seconds, respectively. However, since most of the nanoparticles are not intrinsically fluorescent, such an experiment requires special preparation of the nanomaterial.…”

Atomistic Molecular Dynamics Simulations of Lipids Near TiO2 Nanosurfaces

“… 27 , 28 Exposure to TiO 2 NPs can cause lung inflammation and increased blood coagulation connected with cardiovascular diseases. 23 , 24 Although many possible adverse outcomes of TiO 2 NPs exposure are known, the molecular mechanisms of the nanotoxicity are uncertain. 29 , 30 To study the nanotoxicity mechanisms, a large number of experimental studies on model systems were carried out.…”