The role of surface functionalization on the pulmonary inflammogenicity and translocation into mediastinal lymph nodes of graphene nanoplatelets in rats

Abstract

Graphene, a two-dimensional monocrystalline layer of carbon atoms, has potential in many applications not only in material sciences, but also in the biomedical fields, but there is little information about the role of surface modification on the toxicity of graphene-based nanomaterials. Here, we evaluated the role of surface functionalization of the graphene nanoplatelets (GNPs) on the pulmonary inflammogenicity and translocation into mediastinal lymph nodes using a rat intratracheal instillation model. Six types of GNPs were used: All types of GNPs were based on the pristine GNPs (GNP), and different functional groups were conjugated onto them including a COOH (GNP), COH [Formula: see text], N-H [Formula: see text], F (GNP), and N=H [Formula: see text]. All types of GNPs showed very high potential for the generation of reactive oxygen species (ROS) in a dose-dependent manner when measured by a 2'7'-dichlorofluorescin diacetate assay. GNPs were instilled into the lungs of rats at 0.3 and 1 mg/rat for the evaluation of acute (24 h) inflammation and at 3 mg/rat for chronic (1 and 4 weeks) inflammation. At 24 h after instillation, all types of GNPs showed good dose-dependent increases in polymorphonuclear leukocytes with a clear dose-dependency although significant increases compared to vehicle control were found only in positively charged GNPs [Formula: see text]. While the acute inflammation in all treatment groups was returned to control levels at 1 and 4 weeks after instillation, GNPs showed similar patterns of translocation into the mediastinal lymph nodes with a higher degree over time. This study implies that the main factors of GNPs for producing lung inflammation are the potential for ROS generation and surface charge. In addition, functional groups on the GNPs might not play an important role in the extrapulmonary translocation into the mediastinal lymph nodes.

Titanium dioxide nanoparticles induce COX-2 expression through ROS generation in human periodontal ligament cells

“…We also the checked the dynamic light scattering based size and zeta potential by Zetasizer Nano ZS (Malvern Instruments Limited, Malvern, UK). The process was previously reported (Cho et al, 2013;Lee et al, 2017a). N-acetyl cysteine (NAC) and β-actin antibody were purchased from Sigma-Aldrich (St. Louis, MO, USA).…”

Occupational exposure to graphene based nanomaterials: risk assessment

“…10 Among the investigated GBMs, on evaluating inflammatory cells and/or inflammatory markers in the bronchoalveolar lavage fluid as indices of lung inflammation, GO appeared to be the most toxic one compared to rGO, GNP or FLG, which appeared to be the least toxic GBM at the pulmonary level. [10][11][12][13][14][15][16][17] In contrast, in a very recent comparative study in male C57BL/6 mice (8 weeks-old), pharyngeal aspiration of GO induced lower toxic effects than rGO. 18 However, it should be noted that the physicochemical properties of the tested materials are not always completely reported in these studies (Table 1), making a direct comparison of the effects of GBMs difficult.…”

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

“…Another pulmonary in vivo study which compared six different surface modifications of GP showed increased oxidative stress and acute inflammation [35]. Moreover, positively-charged GP also showed significant inflammation characterized by the accumulation of neutrophil granulocytes [31]. On the other hand, single-layered graphene oxide platelets did not cause acute cytotoxicity or inflammation in a 3D human lung model and similarly, no acute toxicity was demonstrated after 28 days of in vivo exposure to multi-layered graphene platelets [29,36].…”

“…These non-biodegradable materials could pose a risk, especially for the respiratory system after exposure by inhalation [28]. It has been confirmed that GP, which are up to 25 µm in diameter, can be delivered beyond the ciliated airways and deposited in alveoli, where they can either persist in intercellular spaces, or are internalized by alveolar macrophages [29][30][31]. This may lead to inflammation, disruption of homeostasis, and subsequent fibrosis and tissue damage [28,[32][33][34].…”