Carbon Nanotubes and Other Engineered Nanoparticles Induced Pathophysiology on Mesothelial Cells and Mesothelial Membranes

Abstract

Nanoparticles have great potential for numerous applications due to their unique physicochemical properties. However, concerns have been raised that they may induce deleterious effects on biological systems. There is accumulating evidence that, like asbestos, inhaled nanomaterials of >5 μm and high aspect ratio (3:1), particularly rod-like carbon nanotubes, may inflict pleural disease including mesothelioma. Additionally, a recent set of case reports suggests that inhalation of polyacrylate/nanosilica could in part be associated with inflammation and fibrosis of the pleura of factory workers. However, the adverse outcomes of nanoparticle exposure to mesothelial tissues are still largely unexplored. In that context, the present review aims to provide an overview of the relevant pathophysiological implications involving toxicological studies describing effects of engineered nanoparticles on mesothelial cells and membranes. In vitro studies primarily emphasize on simulating cellular uptake and toxicity of nanotubes on benign or malignant cell lines. On the other hand, in vivo studies focus on illustrating endpoints of serosal pathology in rodent animal models. From a molecular aspect, some nanoparticle categories are shown to be cytotoxic and genotoxic after acute treatment, whereas chronic incubation may lead to malignant-like transformation. At an organism level, a number of fibrous shaped nanotubes are related with features of chronic inflammation and MWCNT-7 is the only type to consistently inflict mesothelioma.

Integration of inflammation, fibrosis, and cancer induced by carbon nanotubes

“…It is plausible that inflammation precedes tumorigenesis, and tumorigenesis and inflammation co-occur during the chronic stage after exposure. Indeed, a number of studies have demonstrated the co-existence of inflammation and malignancy in CNT-exposed animals, suggesting an association between inflammation and cancer induced by CNTs (Tables 1 and 2) (Kuempel et al 2017; Sinis et al 2018). For instance, when directly instilled into the pleural cavity of mice, long MWCNTs with the length of 85% fibers more than 15 μm, which are similar to long fiber amosite asbestos, resulted in chronic inflammation and mesotheliomas in the pleura (Chernova et al 2017).…”

“…In these scenarios, the newly synthesized fibrotic ECM from fibrosis creates a tumorigenic microenvironment that boosts tumorigenesis in CNT-deposited tissues, and tumor progression and metastasis in nearby and distal tissues, respectively. Notably, MWCNTs that induce severe fibrosis have a higher capability to induce tumorigenesis than those that cannot, or only slightly, induce fibrosis (Kuempel et al 2017; Sinis et al 2018). For instance, intraperitoneal injection of MWNT-7 induced fibrosis on the liver surface in rats 1-month post-exposure, whereas injection of tangled MWCNTs did not.…”

Clinical Applications of Carbon Nanomaterials in Diagnostics and Therapy

“…A number of studies in plants have identified that CNTs can accumulate in the roots and leaves of plants and induce oxidative stress and photosynthetic defects . Similar oxidative and cellular stress effects have been observed in mammalian cells in vitro . There is also preclinical evidence that inhalation of CNTs and other carbon nanomaterials, such as CNFs, can form fiber‐like shapes that can result in pulmonary diseases similar to asbestos exposure, such as mesothelium .…”

Do Carbon Nanotubes and Asbestos Fibers Exhibit Common Toxicity Mechanisms?

“…Among the highly expressed genes, COX-2 is mainly associated with cell proliferation and inhibition of apoptosis [ 165 , 166 , 167 ]. Many other inflammatory genes such as TNF-α, IL-8 and IL-1β are also regulated after exposure to CNTs and other long fibers [ 168 , 169 ]. In a comprehensive study on the effects of pulmonary exposure to 10 commercial MWCNTs, Poulsen and co-workers found that inflammation and genotoxicity were related to dose, time and physicochemical properties [ 170 ].…”