title: 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 (GNPdot), and different functional groups were conjugated onto them including a COOH (GNPCOOH), COH [Formula: see text], N-H [Formula: see text], Fx(GNPF), 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.
authors.affiliation: Division of Toxicological Research, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Osong, Cheongju, 363-700, Republic of Korea.
authors.forename: Jong Kwon
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Division of Toxicological Research, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Osong, Cheongju, 363-700, Republic of Korea.
authors.forename: A Young
authors.initials: AY
authors.lastname: Jeong
authors.affiliation: Division of Toxicological Research, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Osong, Cheongju, 363-700, Republic of Korea.
authors.forename: Jiyeong
authors.initials: J
authors.lastname: Bae
authors.affiliation: Division of Toxicological Research, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Osong, Cheongju, 363-700, Republic of Korea.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Seok
authors.affiliation: Division of Toxicological Research, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Osong, Cheongju, 363-700, Republic of Korea.
authors.forename: Jun-Young
authors.initials: JY
authors.lastname: Yang
authors.affiliation: Division of Toxicological Research, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Osong, Cheongju, 363-700, Republic of Korea.
authors.forename: Hang Sik
authors.initials: HS
authors.lastname: Roh
authors.affiliation: Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan, 604-714, Republic of Korea.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Jeong
authors.affiliation: Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan, 604-714, Republic of Korea.
authors.forename: Youngju
authors.initials: Y
authors.lastname: Han
authors.affiliation: Division of Toxicological Research, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Osong, Cheongju, 363-700, Republic of Korea. 0jjy@korea.kr.
authors.forename: Jayoung
authors.initials: J
authors.lastname: Jeong
authors.affiliation: Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan, 604-714, Republic of Korea. wcho@dau.ac.kr.
authors.forename: Wan-Seob
authors.initials: WS
authors.lastname: Cho
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006108:Graphite / Q000737:chemistry / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000187:drug effects* / Q000473:pathology; D049329:Nanostructures / Q000737:chemistry* / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013499:Surface Properties; D018675:Toxicity Tests / Q000379:methods
chemical_list: D017382:Reactive Oxygen Species; D006108:Graphite; D007770:L-Lactate Dehydrogenase
keywords: Graphene nanoplatelet; Mediastinal lymph node; Pulmonary inflammation; Reactive oxygen species; Surface functionalization; Toxicity; Translocation