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

Abstract

Carbon nanotubes (CNTs) are nanomaterials with unique physicochemical properties that are targets of great interest for industrial and commercial applications. Notwithstanding, some characteristics of CNTs are associated with adverse outcomes from exposure to pathogenic particulates, raising concerns over health risks in exposed workers and consumers. Indeed, certain forms of CNTs induce a range of harmful effects in laboratory animals, among which inflammation, fibrosis, and cancer are consistently observed for some CNTs. Inflammation, fibrosis, and malignancy are complex pathological processes that, in summation, underlie a major portion of human disease. Moreover, the functional interrelationship among them in disease pathogenesis has been increasingly recognized. The CNT-induced adverse effects resemble certain human disease conditions, such as pneumoconiosis, idiopathic pulmonary fibrosis (IPF), and mesothelioma, to some extent. Progress has been made in understanding CNT-induced pathologic conditions in recent years, demonstrating a close interconnection among inflammation, fibrosis, and cancer. Mechanistically, a number of mediators, signaling pathways, and cellular processes are identified as major mechanisms that underlie the interplay among inflammation, fibrosis, and malignancy, and serve as pathogenic bases for these disease conditions in CNT-exposed animals. These studies indicate that CNT-induced pathological effects, in particular, inflammation, fibrosis, and cancer, are mechanistic-ally, and in some cases, causatively, interrelated. These findings generate new insights into CNT adverse effects and pathogenesis and provide new targets for exposure monitoring and drug development against inflammation, fibrosis, and cancer caused by inhaled nanomaterials.

Microenvironmental Alterations in Carbon Nanotube-Induced Lung Inflammation and Fibrosis

“…The chronic immune outcome is dominated by type 2 response, in which alternatively activated M2 macrophages are enriched and activated (Dong and Ma, 2018b). In summary, the pulmonary responses to CNT exposure initiate from acute inflammatory and fibrotic events, and progress to chronic inflammation and fibrosis (Dong and Ma, 2019b). The biphasic process of CNTinduced lesions resembles that elicited by the deposition of fibrogenic foreign bodies, such as insoluble dusts and large biologic masses, in the lung.…”

“…Remarkable acute immune response is induced in CNTexposed lungs, which precedes and accompanies acute fibrotic response. This phenomenon is reminiscent of inflammationdriven fibrosis occurring in many human diseases, such as IPF, COPD, and systemic sclerosis (Dong and Ma, 2019b). CNTexposed lungs therefore provide a model system to study the role of inflammation in the initiation and progression of fibrosis development, which cannot be performed in other fibrosis models due to the lack of marked acute immune response therein.…”

“…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). To manifest the underpinning systemic, cellular, and molecular events that may function in the development of pathologic inflammation and fibrosis in CNT-exposed lungs, in this article, the major tissue microenvironmental alterations that are induced and function during the acute and chronic phase responses, including effector cells, soluble mediators, and functional events exemplified by immune cell polarization, fibroblast-tomyofibroblast differentiation, and ECM modification, are focused on for discussion.…”

Recent Advances in Nanocarrier-Assisted Therapeutics Delivery Systems

“…In terms of the safety profile of the CNTs, studies suggested that endocytosis of the CNTs induces oxidative stress to the cells, revealing a close connection between CNTs and inflammation, fibrosis, and cancer, impeding the translational value of this nanocarrier [41,42]. In addition, the toxicity of CNTs is not only related to their shape but also to their surface charge [40,[43][44][45][46].…”

<p>The Applications of Carbon Nanotubes in the Diagnosis and Treatment of Lung Cancer: A Critical Review</p>

“…In animal research, CNT-long exposure could induce persistent inflammation, lung cancer, fibrosis, and gene destruction in the lung. 23,24 In general, the mechanisms of creating toxicity are divided into five sections as apoptosis, reactive oxygen species, free radical formation, the formation of granuloma, and increased inflammatory response. Due to the above mechanisms, types of toxicities in cells, skin, gene, liver, cardiovascular, pulmonary, and carcinogens substance, are created.…”