Comparative biodegradation of functionalized graphene oxide nanosheets by myeloperoxidase and neutrophil extracellular traps

Journal article, 2026

Introduction Graphene oxide (GO) nanosheets have attracted significant interest as potential carriers for drug delivery due to their unique physicochemical properties and large surface area. However, concerns regarding their cytotoxicity and biodegradability must be addressed before clinical translation. In this study, we aimed to evaluate the biocompatibility and biodegradation of GO functionalized with polyethylene glycol (PEG) and polyethyleneimine (PEI), two commonly used polymers in biomedical applications.Method The interactions of GO, GO-PEG, and GO-PEI with granulocyte-like cells were investigated to determine their effects on cell viability and their susceptibility to immune-mediated degradation. Biodegradation of the materials was assessed using Raman spectroscopy after exposure to granulocyte-like cells, neutrophil extracellular traps (NETs), and myeloperoxidase (MPO), a key enzyme present in NETs. In addition, circular dichroism (CD) spectroscopy was used to evaluate structural changes in MPO upon interaction with the materials, and molecular dynamics simulations were performed to investigate the interaction of hypochlorous acid (HOCl), the catalytic product of MPO, with GO and its functionalized derivatives.Results and discussion The results showed that functionalization with PEG or PEI significantly improved cell viability compared with pristine GO. Although GO was structurally modified by granulocyte-like cells, NETs, and MPO, GO-PEG did not show significant degradation under these conditions. In contrast, GO-PEI was susceptible to structural modification by both NETs and MPO. CD analysis indicated that MPO maintained a more stable secondary structure in the presence of GO-PEI compared with GO or GO-PEG under oxidative conditions, suggesting that MPO-generated HOCl may play a key role in GO-PEI degradation. Molecular dynamics simulations further demonstrated stronger interaction and retention of HOCl in GO-PEG and GO-PEI systems compared with pristine GO, indicating an enhanced interaction between oxidants and the functionalized materials. Overall, these findings demonstrate that polymer functionalization significantly influences the biocompatibility and immune-mediated structural modification of GO. Importantly, this study provides new mechanistic insights into how PEG and PEI modifications affect MPO-driven oxidative degradation pathways of graphene oxide-based nanomaterials. These results highlight GO-PEI as a biodegradable and biocompatible candidate for future biomedical and drug delivery applications.