Mechanism of Nanoformulated Graphene Oxide-Mediated Human Neutrophil Activation

• Published in: ACS applied materials & interfaces 2020-09, Vol.12 (36), p.40141-40152
• Main Authors: Lu, Yu-Jen, Wang, Yi-Hsuan, Sahu, Rama Shanker, Chen, Jyh-Ping, Dash, Banendu Sunder, Chung, Pei-Jen, Yang, Hung-Wei, Chuang, Er-Yuan, Hwang, Tsong-Long
• Format: Article
• Language: English
• Subjects: Adult; Biocompatible Materials - chemical synthesis; Biocompatible Materials - chemistry; Biocompatible Materials - pharmacology; Biological and Medical Applications of Materials and Interfaces; CD11b Antigen - biosynthesis; Graphite - chemical synthesis; Graphite - chemistry; Graphite - pharmacology; Humans; Nanoparticles - chemistry; Neutrophil Activation - drug effects; Neutrophil Activation - immunology; Neutrophils - drug effects; Neutrophils - immunology; Particle Size; Reactive Oxygen Species - immunology; Surface Properties; Young Adult
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.0c12490

Understanding the molecular mechanisms of graphene oxide (GO)-based biomaterials is important for logical biomedical applications. Previous studies have revealed biointeractions between GO and immune effector cells, but the effects on neutrophils, crucial cells in the immune system, have not been thoroughly discussed. In this study, GO nanoformulations were synthesized with different functional groups, including GO, GO-carboxylated (GO-COOH), and PEGylated GO (GO-PEG), with different surface features, which were elucidated using imaging methods and surface-sensitive quantitative spectroscopic techniques, including atomic force microscopy (AFM), transmission electron microscopy (TEM), and X-ray photoemission spectroscopy (XPS). The GO-based nanoformulations elicited reactive oxygen species (ROS) generation and neutrophil extracellular trap (NET) formation in human neutrophils. Nanoformulated GO stimulates NET development via the formation of ROS. An endocytosis study revealed that nanoformulated GO facilitated internalization by neutrophils via macropinocytosis and actin-dependent phagocytosis. Importantly, calcium mobilization and phosphorylation proteins such as mitogen-activated protein kinases (extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38) and AKT were involved in the activation of neutrophils. These findings offer the first verification that nanoformulated GO exhibits direct effects on human neutrophils.