Toxicity, uptake, and nuclear translocation of ingested micro-nanoplastics in an in vitro model of the small intestinal epithelium

• Published in: Food and chemical toxicology 2021-12, Vol.158, p.112609-112609, Article 112609
• Main Authors: DeLoid, Glen M., Cao, Xiaoqiong, Bitounis, Dimitrios, Singh, Dilpreet, Llopis, Paula Montero, Buckley, Brian, Demokritou, Philip
• Format: Article
• Language: English
• Subjects: Actins; Biological Transport; Caco-2 Cells; Cell Nucleus; Endocytosis; Environmental Exposure - adverse effects; Epithelial Cells - metabolism; HT29 Cells; Humans; Ingestion; Intestinal Mucosa - metabolism; Intestine, Small - metabolism; Microplastics; Microplastics - metabolism; Microplastics - toxicity; Microspheres; Nanostructures; Optical Imaging; Particle Size; Permeability; Polyethylene; Polyethylene - chemistry; Polystyrene; Polystyrenes - metabolism; Polystyrenes - toxicity; Toxicity; Water Pollutants, Chemical - metabolism; Water Pollutants, Chemical - toxicity
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2021.112609

Despite mounting evidence of increasing micro- and nanoplastics (MNPs) in natural environments, food, and drinking water, little is known of the potential health hazards of MNPs ingestion. We assessed toxicity and uptake of environmentally relevant MNPs in an in vitro small intestinal epithelium (SIE). Test MNPs included 25 and 1000 nm polystyrene (PS) microspheres (PS25 and PS1K); 25, 100, and 1000 nm carboxyl modified PS spheres (PS25C, PS100C, and PS1KC), and secondary MNPs from incinerated polyethylene (PEI). MNPs were subjected to 3-phase digestion to mimic transformations in the gastrointestinal tract (GIT) and digestas applied to the SIE. Carboxylated MNPs significantly reduced viability and increased permeability to 3 kD dextran. Uptake of carboxyl PS materials was size dependent, with significantly greater uptake of PS25C. Fluorescence confocal imaging showed some PS25C agglomerates entering cells independent of endosomes (suggesting diffusion), others within actin shells (suggesting phagocytosis), and many free within the epithelial cells, including agglomerates within nuclei. Pre-treatment with the dynamin inhibitor Dyngo partially reduced PS25 translocation, suggesting a potential role for endocytosis. These findings suggest that ingestion exposures to MNPs could have serious health consequences and underscore the urgent need for additional detailed studies of the potential hazards of ingested MNPs. [Display omitted] •Carboxylated polystyrene micro-nanospheres impaired viability and barrier function.•Carboxylated polystyrene nanospheres readily entered and crossed the epithelium•Nanospheres were localized throughout the cytoplasm and within cell nuclei.•Dynamin inhibition reduced translocation, suggesting some uptake by endocytosis.•Some nanospheres were seen in actin shells, suggesting entry by phagocytosis. Synopsis: A study of ingested micro-nanoplastics (MNPs) in an in vitro small intestinal epithelium model revealed significant direct toxicity and the ability of nanoscale MNPs to enter and move through and throughout in vitro enterocytes, including their nuclei, suggesting potential serious health implications from ingestion exposures to MNPs—which are accumulating in natural environments as a result of the enormous (and exponentially increasing) amounts of plastics produced and used in the last century—highlighting the urgent need for further studies and for policy measures aimed at curbing production and use of petroleum-based plastics,