Cadmium co-ingestion promotes systemic nanoplastics distribution in mice via multi-level intestinal barrier compromise

Nanoplastics (NPs) have been detected in global ecosystem, raising serious concerns about their potential health risks. Oral exposure is recognized as the primary route of human NPs exposure, but the mechanisms of absorption, translocation, and toxic effects and the influencing factors (particularly co-existing contaminants) remain poorly understood. Through a 35-day oral administration, it was found that co-exposure to Cd facilitates systemic distribution of polystyrene NPs in mouse models, resulting in synergistic and irreversible toxicological effects. Specifically, the Cd exposure compromises intestinal barrier function by disrupting the mucus layer and inducing intercellular tight junctions opening, thereby enhancing NPs phagocytosis by macrophages and triggering systemic immune activation. This pathological cascade leads to intestinal barrier dysfunction, facilitating NPs translocation across the intestinal barrier and subsequent distribution in multiple organs, including liver, lung, kidney, heart, and even brain, thereby exacerbating injury to extraintestinal organs. Notably, the synergistic effects between Cd and NPs persist after 4-week recovery and across diverse surface properties. These findings underscore that co-existing contaminants can markedly aggravate the health risks associated with NPs even at environmentally relevant concentrations, highlighting the imperative for comprehensive risk assessment and management strategies to address the intricate interactions of NPs in real-world scenarios.