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

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• 作者：Jong Kwon Lee ; A Young Jeong ; Jiyeong Bae ; Ji Hyun Seok…
• 关键词：Graphene nanoplatelet ; Surface functionalization ; Reactive oxygen species ; Pulmonary inflammation ; Translocation ; Toxicity ; Mediastinal lymph node
• 刊名：Archives of Toxicology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：91
• 期：2
• 页码：667-676
• 全文大小：
• 刊物主题：Pharmacology/Toxicology; Occupational Medicine/Industrial Medicine; Environmental Health; Biomedicine, general;
• 出版者：Springer Berlin Heidelberg
• ISSN：1432-0738
• 卷排序：91

文摘

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_dot), and different functional groups were conjugated onto them including a COOH (GNP_COOH), COH \(\left( {{\text{GNP}}_{{{\text{O}}_{2} }} } \right)\), N–H \(\left( {{\text{GNP}}_{{{\text{N}}_{2} }} } \right)\), F_x (GNP_F), and N=H \(\left( {{\text{GNP}}_{{{\text{NH}}_{2} }} } \right)\). 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 \(\left( {{\text{GNP}}_{{{\text{N}}_{2} }} \;{\text{and}}\;{\text{GNP}}_{{{\text{NH}}_{2} }} } \right)\). 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.