Effect of PEGylated Graphene Oxide Nanoparticles on the Functions and Metabolism of THP ‐1 Cells

ABSTRACT Graphene oxide (GO) nanoparticles hold biomedical promise due to unique properties, but their immunomodulatory effects on phagocytes require evaluation, particularly regarding size‐ and coating‐dependent interactions. Polyethylene glycol (PEG) coatings reduce cytotoxicity, yet long‐term impacts of varied coatings remain critical. This study investigated PEGylated GO nanoparticles (P‐GO) of two lateral sizes (≈100–300 nm and ≈1–1.5 μm) with linear or branched PEG coatings on THP‐1 monocyte viability, apoptosis, metabolism, and wide‐spectrum cytokine production. Only the larger branched PEG‐coated GO (25 μg/mL) exhibited cytotoxicity after 72 h. Other variants showed no cytotoxicity but modulated THP‐1 activity. Larger linear PEG‐coated GO induced apoptosis within 24 h. All particles in a concentration of 25 μg/mL were internalized by/adhered to cells, suppressed ROS production, and altered cytokine profiles: TNF‐α, MIP‐1β, MIP‐1α, and G‐CSF increased, while HGF and SCGF‐β decreased. Larger branched PEG‐coated GO suppressed oxidative phosphorylation and glycolysis after 24 h. While a spectrum of effects of PEGylated graphene oxide on THP‐1 cell functions was identified, predominantly observed at a dose of 25 μg/mL over a 24 to 72‐h exposure period, no clear dependence of P‐GO nanoparticle effects on THP‐1 cells was observed with respect to PEG coating type (linear vs. branched) or particle size. At 5 μg/mL, P‐GO caused minimal functional modulation. Thus, the study underscores the potential of low‐concentration P‐GO for therapeutic use while cautioning that even non‐cytotoxic nanoparticles can profoundly alter immune cell behavior.