Size-Associated Partitioning of Oral Polystyrene Particles Between Intestinal Capillaries and Lacteals Determines Systemic and Lymph Node Distribution in Mice

Micro- and nanoplastics are widespread environmental contaminants; however, the intestinal routes governing their entry into systemic circulation remain unclear. Here, we used commercially available fluorescently labeled spherical polystyrene (PS) particles as a model system to investigate the intestinal transport of 100, 500 and 1000 nm particles in mice. We combined whole-mount imaging of intestinal villi with blood and organ kinetic analyses, mesenteric imaging and modulation of lacteal endothelial junctions. The whole-blood concentration of 100 nm particles peaked at 1 h, followed by peak liver and kidney fluorescence at 2 h. In contrast, 500 and 1000 nm particles preferentially localized to lacteals and mesenteric lymphatic vessels, accumulated more strongly in mesenteric lymph nodes and showed delayed blood and organ peaks at 6 h. Shifting lacteal junction organization from discontinuous button-like junctions toward continuous zipper-like junctions with the Rho-associated kinase inhibitor Y-27632 reduced the lymph node accumulation of the larger particles, supporting a functional role for lacteal permeability in their uptake and downstream transport. Repeated exposure to the corresponding unmodified PS particles was associated with lower body weight at day 30, as well as mesenteric lymph node enlargement and cellular disorganization. These lymph node alterations were accompanied by increased mRNA expression of the pro-inflammatory cytokine genes Ifng, Il1b and Tnf, consistent with a local inflammatory response. Together, these findings demonstrate size-associated partitioning of orally administered PS model particles between intestinal blood and lymphatic routes and provide a framework linking intestinal entry with subsequent systemic distribution, while identifying local mesenteric lymph node responses following repeated exposure.