In vitro and in vivo comparison of the immunotoxicity of single- and multi-layered graphene oxides with or without pluronic F-127

Abstract

Graphene oxide (GO) has been a focus of research in the fields of electronics, energy, and biomedicine, including drug delivery. Thus, single- and multi-layered GO (SLGO and MLGO) have been produced and investigated. However, little information on their toxicity and biocompatibility is available. In the present study, we performed a comprehensive study of the size- and dose-dependent toxicity of GOs in the presence or absence of Pluronic F-127 on THP-1 cells by examining their viability, membrane integrity, levels of cytokine and ROS production, phagocytosis, and cytometric apoptosis. Moreover, as an extended study, a toxicity evaluation in the acute and chronic phases was performed in mice via intravenous injection of the materials. GOs exhibited dose- and size-dependent toxicity. Interestingly, SLGO induced ROS production to a lesser extent than MLGO. Cytometric analysis indicated that SLGO induced necrosis and apoptosis to a lesser degree than MLGO. In addition, cell damage and IL-1β production were influenced by phagocytosis. A histological animal study revealed that GOs of various sizes induced acute and chronic damage to the lung and kidney in the presence or absence of Pluronic F-127. These results will facilitate studies of GO prior to its biomedical application.

Graphene Oxide Elicits Membrane Lipid Changes and Neutrophil Extracellular Trap Formation

“…These results support the emerging view that the toxicity of GO could be related to its effects on the plasma membrane 25,29,73 and provide direct experimental evidence of lipid perturbations in cells exposed to GO. This does not exclude a role for phagocytosis-associated cellular effects, 74 but the data suggest that large, micrometer-sized GO sheets, in particular, may act directly on the cell membrane. Notably, the adjuvant, alum, was previously shown to trigger responses in DCs by altering membrane lipid structures, demonstrating that not all immune signaling is receptor mediated and implying that the plasma membrane may behave as a sensor for solid structures.…”

Developmental neurotoxicity and immunotoxicity induced by graphene oxide in zebrafish embryos

“…We initially measured the extent of cytotoxicity caused by GO to RAW264.7 cells. Effective cell death was observed upon the treatment of 0.1‐10 μg/mL GO for 24 hours (Supporting Information Figure S6), which were also observed in THP‐1 cells . Following the mRNA levels of TNFα and IL‐8 in RAW264.7 cells after 24 hours GO exposure was then examined.…”

Main trends of immune effects triggered by nanomedicines in preclinical studies

“…[16][17][18][19] The inflammatory reactions were almost exclusively induced by inorganic NPs, mainly carbon-based or metal-based NPs, in particular, titanium dioxide NPs, gold NPs, 20,21 silica NPs 22 and graphene oxidebased nanomaterials. 23,24 An important component of the innate immune defense consists of the macrophages covering heterogeneous population of phagocytic cells. Their function is to recognize and engulf foreign bodies including pathogens and cell debris.…”

“…• Activation of inflammatory pathways 17,24,27 • Histopathology 20,23,55 • Production of ROS and RNS 22,119,120 Rodents Partially covered by ICH S8 as a part of STS…”