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      Cellular Toxicity and Immunological Effects of Carbon-based Nanomaterials

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          Abstract

          Background

          Carbon nanomaterials are a growing family of materials featuring unique physicochemical properties, and their widespread application is accompanied by increasing human exposure.

          Main body

          Considerable efforts have been made to characterize the potential toxicity of carbon nanomaterials in vitro and in vivo. Many studies have reported various toxicology profiles of carbon nanomaterials. The different results of the cytotoxicity of the carbon-based materials might be related to the differences in the physicochemical properties or structures of carbon nanomaterials, types of target cells and methods of particle dispersion, etc. The reported cytotoxicity effects mainly included reactive oxygen species generation, DNA damage, lysosomal damage, mitochondrial dysfunction and eventual cell death via apoptosis or necrosis. Despite the cellular toxicity, the immunological effects of the carbon-based nanomaterials, such as the pulmonary macrophage activation and inflammation induced by carbon nanomaterials, have been thoroughly studied. The roles of carbon nanomaterials in activating different immune cells or inducing immunosuppression have also been addressed.

          Conclusion: Here, we provide a review of the latest research findings on the toxicological profiles of carbon-based nanomaterials, highlighting both the cellular toxicities and immunological effects of carbon nanomaterials. This review provides information on the overall status, trends, and research needs for toxicological studies of carbon nanomaterials.

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          Most cited references170

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          Nanotoxicology: An Emerging Discipline Evolving from Studies of Ultrafine Particles

          Although humans have been exposed to airborne nanosized particles (NSPs; < 100 nm) throughout their evolutionary stages, such exposure has increased dramatically over the last century due to anthropogenic sources. The rapidly developing field of nanotechnology is likely to become yet another source through inhalation, ingestion, skin uptake, and injection of engineered nanomaterials. Information about safety and potential hazards is urgently needed. Results of older bio-kinetic studies with NSPs and newer epidemiologic and toxicologic studies with airborne ultrafine particles can be viewed as the basis for the expanding field of nanotoxicology, which can be defined as safety evaluation of engineered nanostructures and nanodevices. Collectively, some emerging concepts of nanotoxicology can be identified from the results of these studies. When inhaled, specific sizes of NSPs are efficiently deposited by diffusional mechanisms in all regions of the respiratory tract. The small size facilitates uptake into cells and transcytosis across epithelial and endothelial cells into the blood and lymph circulation to reach potentially sensitive target sites such as bone marrow, lymph nodes, spleen, and heart. Access to the central nervous system and ganglia via translocation along axons and dendrites of neurons has also been observed. NSPs penetrating the skin distribute via uptake into lymphatic channels. Endocytosis and biokinetics are largely dependent on NSP surface chemistry (coating) and in vivo surface modifications. The greater surface area per mass compared with larger-sized particles of the same chemistry renders NSPs more active biologically. This activity includes a potential for inflammatory and pro-oxidant, but also antioxidant, activity, which can explain early findings showing mixed results in terms of toxicity of NSPs to environmentally relevant species. Evidence of mitochondrial distribution and oxidative stress response after NSP endocytosis points to a need for basic research on their interactions with subcellular structures. Additional considerations for assessing safety of engineered NSPs include careful selections of appropriate and relevant doses/concentrations, the likelihood of increased effects in a compromised organism, and also the benefits of possible desirable effects. An interdisciplinary team approach (e.g., toxicology, materials science, medicine, molecular biology, and bioinformatics, to name a few) is mandatory for nanotoxicology research to arrive at an appropriate risk assessment.
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            The potential environmental impact of engineered nanomaterials.

            With the increased presence of nanomaterials in commercial products, a growing public debate is emerging on whether the environmental and social costs of nanotechnology outweigh its many benefits. To date, few studies have investigated the toxicological and environmental effects of direct and indirect exposure to nanomaterials and no clear guidelines exist to quantify these effects.
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              Comparative pulmonary toxicity assessment of single-wall carbon nanotubes in rats.

              The aim of this study was to evaluate the acute lung toxicity of intratracheally instilled single-wall carbon nanotubes (SWCNT) in rats. The lungs of rats were instilled either with 1 or 5 mg/kg of the following control or particle types: (1) SWCNT, (2) quartz particles (positive control), (3) carbonyl iron particles (negative control), (4) phosphate-buffered saline (PBS) + 1% Tween 80, or (5) graphite particles (lung tissue studies only). Following exposures, the lungs of PBS and particle-exposed rats were assessed using bronchoalveolar lavage (BAL) fluid biomarkers and cell proliferation methods, and by histopathological evaluation of lung tissue at 24 h, 1 week, 1 month, and 3 months postinstillation. Exposures to high-dose (5 mg/kg) SWCNT produced mortality in ~15% of the SWCNT-instilled rats within 24 h postinstillation. This mortality resulted from mechanical blockage of the upper airways by the instillate and was not due to inherent pulmonary toxicity of the instilled SWCNT particulate. Exposures to quartz particles produced significant increases versus controls in pulmonary inflammation, cytotoxicity, and lung cell parenchymal cell proliferation indices. Exposures to SWCNT produced transient inflammatory and cell injury effects. Results from the lung histopathology component of the study indicated that pulmonary exposures to quartz particles (5 mg/kg) produced dose-dependent inflammatory responses, concomitant with foamy alveolar macrophage accumulation and lung tissue thickening at the sites of normal particle deposition. Pulmonary exposures to carbonyl iron or graphite particles produced no significant adverse effects. Pulmonary exposures to SWCNT in rats produced a non-dose-dependent series of multifocal granulomas, which were evidence of a foreign tissue body reaction and were nonuniform in distribution and not progressive beyond 1 month postexposure (pe). The observation of SWCNT-induced multifocal granulomas is inconsistent with the following: (1) lack of lung toxicity by assessing lavage parameters, (2) lack of lung toxicity by measuring cell proliferation parameters, (3) an apparent lack of a dose response relationship, (4) nonuniform distribution of lesions, (5) the paradigm of dust-related lung toxicity effects, (6) possible regression of effects over time. In addition, the results of two recent exposure assessment studies indicate very low aerosol SWCNT exposures at the workplace. Thus, the physiological relevance of these findings should ultimately be determined by conducting an inhalation toxicity study.
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                Author and article information

                Contributors
                dryuanxia@126.com
                2368901856@qq.com
                12695107@qq.com
                yqwei@vip.sina.com
                xiaweiwei@scu.edu.cn
                Journal
                Part Fibre Toxicol
                Part Fibre Toxicol
                Particle and Fibre Toxicology
                BioMed Central (London )
                1743-8977
                11 April 2019
                11 April 2019
                2019
                : 16
                : 18
                Affiliations
                ISNI 0000 0004 1770 1022, GRID grid.412901.f, Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, , West China Hospital, Sichuan University, ; No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan 610041 People’s Republic of China
                Article
                299
                10.1186/s12989-019-0299-z
                6460856
                30975174
                35409058-ec1e-4647-99c9-9e4c021cb5a3
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 8 November 2018
                : 18 March 2019
                Funding
                Funded by: the National Natural Science Foundation of China; the National Key Research and Development Program of China
                Award ID: No. 81602492;No. 2016YFA0201402
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2019

                Toxicology
                cytotoxicity,carbon nanomaterial,macrophage,immunological effects
                Toxicology
                cytotoxicity, carbon nanomaterial, macrophage, immunological effects

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