Polystyrene nanoplastics promote tumor lung metastasis by inducing sodium overload in macrophages in an NMDAR-dependent way

Micro- and nanoplastics (MNPs) are increasingly recognized as ubiquitous environmental pollutants; however, their role in tumor metastasis remains poorly understood. This study aimed to investigate the impact of polystyrene nanoplastics on breast Cancer lung metastasis and to elucidate the underlying mechanisms. Using a mouse model of breast Cancer, we demonstrated that inhalation of amino-modified polystyrene nanoplastics (NPS) significantly increased the number of metastatic nodules in the lungs. Mechanistically, NPS were found to bind integrins on the macrophage membrane and activated membrane-localized N-methyl-D-aspartate receptor (NMDAR), thereby inducing intracellular sodium overload. This process led to macrophage swelling, detachment, and subsequent pulmonary inflammation. Importantly, pharmacological inhibition or genetic knockdown of NMDARs effectively suppressed NPS-induced sodium influx and macrophage death, and markedly alleviated pulmonary inflammation in vivo. Collectively, these findings reveal that nanoplastics promote lung metastasis by disrupting cellular sodium homeostasis and thereby providing new insights into the potential health risks associated with nanoplastics exposure.