Mesoporous carbon nanomaterials induced pulmonary surfactant inhibition, cytotoxicity, inflammation and lung fibrosis

Abstract

Environmental exposure and health risk upon engineered nanomaterials are increasingly concerned. The family of mesoporous carbon nanomaterials (MCNs) is a rising star in nanotechnology for multidisciplinary research with versatile applications in electronics, energy and gas storage, and biomedicine. Meanwhile, there is mounting concern on their environmental health risks due to the growing production and usage of MCNs. The lung is the primary site for particle invasion under environmental exposure to nanomaterials. Here, we studied the comprehensive toxicological profile of MCNs in the lung under the scenario of moderate environmental exposure. It was found that at a low concentration of 10μg/mL MCNs induced biophysical inhibition of natural pulmonary surfactant. Moreover, MCNs at similar concentrations reduced viability of J774A.1 macrophages and lung epithelial A549 cells. Incubating with nature pulmonary surfactant effectively reduced the cytotoxicity of MCNs. Regarding the pro-inflammatory responses, MCNs activated macrophages in vitro, and stimulated lung inflammation in mice after inhalation exposure, associated with lung fibrosis. Moreover, we found that the size of MCNs played a significant role in regulating cytotoxicity and pro-inflammatory potential of this nanomaterial. In general, larger MCNs induced more pronounced cytotoxic and pro-inflammatory effects than their smaller counterparts. Our results provided valuable information on the toxicological profile and environmental health risks of MCNs, and suggested that fine-tuning the size of MCNs could be a practical precautionary design strategy to increase safety and biocompatibility of this nanomaterial.

An adverse outcome pathway for lung surfactant function inhibition leading to decreased lung function

“…The biological plausibility and empirical evidence of the inhibition of lung surfactant function by inhaled substances or by blood components reaching the alveolar airspaces, are high. Studies have been conducted for a number of substances including airborne nanoparticles ( Chen et al, 2017 , Yang et al, 2018 , Larsen et al, 2020 ), airborne chemicals ( Da Silva et al, 2021 ), and biological components such as albumin, cholesterol meconium, and serum ( Zuo et al, 2006 , Lopez-Rodriguez et al, 2011 , Lopez-Rodriguez et al, 2012 , Lopez-Rodriguez et al, 2013 , Zhang et al, 2012 , Autilio et al, 2021 , Gómez-Gil et al, 2009 , Lugones et al, 2018 , Gunasekara et al, 2005 ). For impregnation spray products, the inhibition of lung surfactant function has been reported across multiple methods in vitro , such as the lung surfactant bioassay ( Sørli et al, 2018 ), the capillary surfactometer ( Sørli et al, 2016 ), the pulsating bubble surfactometer ( Tashiro et al, 1998 ), and the Langmuir trough ( Duch et al, 2014 , Larsen, et al, 2014 ).…”

Bilirubin detoxification using different phytomaterials: characterization and in vitro studies

“…By increasing the stability of nano-AC in suspension, adsorption and removal of various toxin molecules will be enhanced. 16,44,45 In order to determine general decomposition characteristics of the raw phytomaterials during activation, samples were subjected to TGA. Figure 5A shows the TGA curves of date pits, jojoba seeds, and microalgae in N 2 atmosphere at a 10°C/minute heating rate.…”

“…40 The variation in conjunction with the different nano-AC products applied could be attributed to the difference in particle size and surface charge (Figures 3 and 4). 44 Furthermore, the MTT assay appeared to be more sensitive, which can be attributed to either the assay being based mainly on the enzymatic conversion of MTT in the mitochondria and/or the reactive oxygen species generated within the mitochondria may also have damaged mitochondrial components. 40 Effect of AC on morphology of THLE2 and hepg2 cells THLE2 and HepG2 cells was stained with DAPI-Fluoroshield and phalloidin-FITC fluorescent dyes ( Figure 11).…”

Fluid Films as Models for Understanding the Impact of Inhaled Particles in Lung Surfactant Layers

“…Particle size is a very important parameter controlling the interaction of particles with cells, affecting particle uptake. Furthermore, particle size affects their cytotoxicity and the induction of inflammatory response [215,216]. Therefore, it may be expected that size can also influence the interaction between inhaled pollutants and the LS film.…”