Macrophage cytoskeletal and immune responses to photoaged and gastrointestinal-transformed polylactic acid micro/nanoplastics with protein corona

Polylactic acid micro/nanoplastics (PLA MNPs) have been shown to pose environmental and health risks; however, knowledge of how environmental photoaging and gastrointestinal exposure pathways influence their plasma protein corona (PC) composition and subsequent biological effects on macrophages remains limited. Our results show that environmental ultraviolet (UV) accelerated aging and further simulated gastrointestinal digestion reduced PLA MNPs size by more than threefold, significantly increased surface negativity, and drove selective plasma protein adsorption through hydrogen bonding and steric hindrance. Specifically, pristine PLA MNPs primarily bound lipoprotein-related proteins, whereas aged and digested forms preferentially bound complement and coagulation proteins. Despite substantial differences in PC composition, exposure to MNPs@PC at a biologically relevant concentration (1 mg/L) consistently induced pronounced cytoskeletal disruptions in THP-1 macrophages, characterized by downregulation of intermediate filament-associated proteins and F-actin disassembly and remodeling. Moreover, MNPs@PC exposure activated immune pathways in THP-1 macrophages and triggered the formation of macrophage extracellular traps (METs). Collectively, these findings provide molecular-level evidence of the potential health risks posed by photoaged and gastrointestinally transformed PLA MNPs following PC formation, highlighting the need for further investigation into their long-term biological effects and implications for human health.