Surface-Oxidized Nanoplastics Exhibit Increased Interaction with THP-1 Cells

Abstract

The environmental and human health implications of microplastics (MPs) and nanoplastics (NPs) have become a growing concern, particularly as increasing evidence demonstrates their accumulation in human tissues and association with disease. However, most toxicological studies rely on spherical polystyrene particles, which poorly represent environmentally relevant MPs and NPs that exhibit irregular morphologies and undergo surface oxidative degradation. In this study, we developed fragmented polyethylene NPs (PE-NPs) with physicochemical properties that better mimic environmental particles. PE-NPs were synthesized via a precipitation-based method and subsequently subjected to vacuum UV irradiation to induce surface oxidation and generate degraded PE-NPs (dPE-NPs). Structural and chemical characterizations confirmed the irregular morphology and successful introduction of carbonyl functional groups without altering the particle shape. Fluorescent labeling using Nile Red enabled the visualization of PE-NPs and revealed oxidation-dependent shifts in fluorescence properties. Using phorbol 12-myristate 13-acetate-differentiated THP-1 macrophage-like cells, we investigated cellular interaction behavior, including particle uptake and particles localized near the cell membrane. Confocal microscopy demonstrated a significantly enhanced cellular interaction of dPE-NPs, including both uptake and particle-associated signals localized near the cell membrane. Quantitative analysis confirmed that surface oxidation markedly increased the particle-associated area per cell. These findings highlight the critical role of surface oxidative modification in governing NP–cell interactions and uptake kinetics. Our results emphasize that physicochemical properties, particularly environmentally induced surface changes, must be considered for realistic risk assessment of NPs. This study provides an environmentally relevant experimental framework and advances our understanding of how NP aging influences biological behavior and potential health risks.