Mechanisms of carbon nanotube‐induced pulmonary fibrosis: a physicochemical characteristic perspective

Abstract

Carbon nanotubes (CNTs) are engineered nanomaterials (ENMs) with numerous beneficial applications. However, they could pose a risk to human health from occupational or consumer exposures. Rodent models demonstrate that exposure to CNTs via inhalation, instillation, or aspiration results in pulmonary fibrosis. The severity of the fibrogenic response is determined by various physicochemical properties of the nanomaterial such as residual metal catalyst content, rigidity, length, aggregation status, or surface charge. CNTs are also increasingly functionalized post-synthesis with organic or inorganic agents to modify or enhance surface properties. The mechanisms of CNT-induced fibrosis involve oxidative stress, innate immune responses of macrophages, cytokine and growth factor production, epithelial cell injury and death, expansion of the pulmonary myofibroblast population, and consequent extracellular matrix accumulation. A comprehensive understanding of how physicochemical properties affect the fibrogenic potential of various types of CNTs should be considered in combination with genetic variability and gain or loss of function of specific genes encoding secreted cytokines, enzymes, or intracellular cell signaling molecules. Here, we cover the current state of the literature on mechanisms of CNT-exposed pulmonary fibrosis in rodent models with a focus on physicochemical characteristics as principal drivers of the mechanisms leading to pulmonary fibrosis. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Respiratory Disease Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials.

Microenvironmental Alterations in Carbon Nanotube-Induced Lung Inflammation and Fibrosis

“…Prompted by the noticeable fibrotic phenotypes triggered by CNTs in the lung, a large body of studies have been performed to elucidate the mechanisms that promote the initiation and progression of lung fibrosis in CNT-exposed animals in recent years, leading to a marked progress in this research area. Importantly, the findings reveal that the systemic, cellular, and molecular mechanisms of CNT-triggered lung fibrosis are consistent with the current knowledge on lung fibrosis derived from the studies on human fibrotic lung diseases and some lung fibrosis animal models, such as bleomycin-induced lung fibrosis, to a considerable extent, indicating CNT-induced lung fibrosis may serve as a new disease model (Dong and Ma, 2016b;Vietti et al, 2016;Dong and Ma, 2018b;Duke and Bonner, 2018). Remarkably, like the scenarios in many human fibrotic lung diseases, inflammation plays a critical role in the onset and progression of lung fibrosis induced by CNT exposure, providing the potential of using CNT-exposed rodents as a unique disease model for lung fibrosis studies (Dong and Ma, 2019b).…”

Proinflammatory Effect of Carbon-Based Nanomaterials: In Vitro Study on Stimulation of Inflammasome NLRP3 via Destabilisation of Lysosomes

“…Even though both CNT and graphene have been extensively investigated over the recent years, the results are still inconsistent and often contradictory. Asbestos-like shape of CNT leads to the assumption that both single and multi-walled carbon nanotubes (SWCNT and MWCNT) have a capacity to induce acute and chronic inflammation [7][8][9]. Depending on the shape, length, functionalization and presence of impurities, the mechanical disruption associated with oxidative stress, mitochondrial damage, and production of pro-inflammatory cytokines are considered principal mechanisms of cytotoxicity [10][11][12].…”

Differential Cytotoxicity Induced by Transition Metal Oxide Nanoparticles is a Function of Cell Killing and Suppression of Cell Proliferation

“…NP-mediated toxicity is a rather complicated process and more factors, other than the ones we have determined, are at work. There have been numerous reports on titanium oxide [19], nanogold [20], carbon nanotubes [21], silica oxide [22], aluminum oxide [15], and cerium oxide [23] relating to cell killing. The final cell number that researchers observed was more than just the effect of cell death.…”