Neutrophils Defensively Degrade Graphene Oxide in a Lateral Dimension Dependent Manner through Two Distinct Myeloperoxidase Mediated Mechanisms

The boosting exploitation of graphene oxide (GO) increases exposure risk to human beings. However, as the first line defender, neutrophils’ mechanism of defensive behavior towards GO invasion remains unclear. Herein, we discover that neutrophils 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 neutrophils’ defensive behavior is accompanied with generation of reactive oxygen species and activation of p-ERK and p-Akt kinases. We unveil that mGO-induced NETosis is NADPH oxidase (NOX)-independent, while nGO-triggered degranulation is NOX-dependent. Furthermore, myeloperoxidase (MPO) is identified to be a determinant mediator despite distinct neutrophil phenotypes in the biodegradation. 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, which indicates that electrostatic interactions mainly cause the spontaneous binding process in a spatial distance of 9.2 Å. Meanwhile, the central enzymatic biodegradation is found to occur at oxygenic active sites and defects on GO. Mass spectrometry analysis deciphers the degradation products are biocompatible molecules like flavonoids and polyphenols. Our study provides fundamental evidence and practical guidance for functional biomaterial development in sustainable nanotechnology, including but not limited to vaccine adjuvant and drug carrier.