Encountering and Wrestling: Neutrophils Recognize and Defensively Degrade Graphene Oxide

Abstract

The boosting exploitation of graphene oxide (GO) increases exposure risk to human beings. However, as primary defender in the first immune line, neutrophils' mechanism of defensive behavior toward GO remains unclear. Herein, we discovered that neutrophils recognize and defensively degrade GO in a lateral dimension dependent manner. The micrometer-sized GO (mGO) induces NETosis by releasing neutrophil extracellular traps (NETs), while nanometer-sized GO (nGO) elicits neutrophil degranulation. The two neutrophils' defensive behaviors are accompanied with generation of reactive oxygen species and activation of p-ERK and p-Akt kinases. However, mGO-induced NETosis is NADPH oxidase (NOX)-independent while nGO-triggered degranulation is NOX-dependent. Furthermore, myeloperoxidase (MPO) is determinant mediator despite distinct neutrophil phenotypes. Neutrophils release NETs comprising of MPO upon activated with mGO, while MPO is secreted via nGO-induced degranulation. Moreover, the binding energy between MPO and GO is calculated to be 69.8728 kJ mol −1 , indicating that electrostatic interactions mainly cause the spontaneous binding process. Meanwhile, the central enzymatic biodegradation occurs at oxygenic active sites and defects on GO. Mass spectrometry analysis deciphers the degradation products are biocompatible molecules like flavonoids and polyphenols. This study provides fundamental evidence and practical guidance for nanotechnology based on GO, including vaccine adjuvant, implantable devices, and energy storage.

Biodegradation of Graphene Oxide by Insects (Tenebrio molitor Larvae): Role of the Gut Microbiome and Enzymes

“…The degradation of GO sheets should have started from the oxygen-containing groups (e.g., carboxyl group and epoxy group) at the edge, but the decomposition degree on the main graphitic structure was not obvious as indicated from the low mineralization rate (Figure ). A decrease in oxygen content on the graphitic structure was also found in the biodegradation of GO by other bacteria (Shewanella) and neutrophils, , which are in good agreement with our findings. In addition to CO 2 , small fragments and low-molecular-weight organic byproducts (Figure S14) were also formed during the oxidation process (Figure B).…”

“…Two hydroxyl groups were thus formed during the opening of epoxy rings in the presence of the hydroxyl radical. , This process could also explain the slight increase in O content on the residual GO film of frass (Table S2). As one of the most powerful oxidizing agents, hydroxyl radicals (e.g., generated from gut extracellular enzymes) were capable of converting hydroxyl groups to carbonyl groups and further oxidized into carboxyl groups . Then, a fraction of the formed carboxyl groups was transformed into CO 2 via decarboxylation.…”

“…As one of the most powerful oxidizing agents, hydroxyl radicals (e.g., generated from gut extracellular enzymes) were capable of converting hydroxyl groups to carbonyl groups and further oxidized into carboxyl groups. 52 Then, a fraction of the formed carboxyl groups was transformed into CO 2 via decarboxylation. The degradation of GO sheets should have started from the oxygen-containing groups (e.g., carboxyl group and epoxy group) at the edge, 49 but the decomposition degree on the main graphitic structure was not obvious as indicated from the low mineralization rate (Figure 2).…”

Immunotoxicity of Carbon-Based Nanomaterials, Starring Phagocytes

“…Formation of NETs after exposition of mouse bone-derived neutrophils to micro-sized GO was also confirmed in another study. The authors also pointed out the importance of size, where nano-sized GO predominantly induced neutrophils degranulation [ 136 ]. So far, GO has been one of the most studied NMs due to its potential in nanomedicine.…”

Precise Design Strategies of Nanotechnologies for Controlled Drug Delivery

“…Over the past decade, nanotechnologies based on carbon materials, including carbon nanotube (CNT) [ 87 ], graphene and its derivatives [ 88 ], and carbon dots (CDs) [ 89 ], have aroused in the biomedical application. The surface area of carbon materials possesses high potential of functionalization and modification, which may enhance the solubility, stability, and biocompatibility in physiological environment.…”