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Macrophage cytoskeletal and immune responses to photoaged and gastrointestinal-transformed polylactic acid micro/nanoplastics with protein corona
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Researchers found that UV photoaging and simulated gastrointestinal digestion shrank polylactic acid micro/nanoplastics to one-third their original size and shifted their surface protein corona from lipoprotein-binding to complement and coagulation proteins, yet both pristine and aged particles consistently disrupted the cytoskeleton of human macrophages and triggered formation of macrophage extracellular traps.
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.
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When polystyrene nano- and microplastics pass through simulated gastrointestinal digestion, they acquire a coating of gut proteins — a 'protein corona' — that dramatically increases their uptake by human immune cells (macrophages), boosting internalization of small neutral particles by up to six-fold compared to undigested plastic. The identity of the proteins driving this effect, including clotting factors and apolipoproteins, suggests that realistic dietary exposure conditions substantially change how microplastics interact with the body, and that lab tests using undigested plastics likely underestimate actual cellular uptake.
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