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Polystyrene nanoplastics promote tumor lung metastasis by inducing sodium overload in macrophages in an NMDAR-dependent way
Summary
Breathing in tiny plastic particles (nanoplastics) may make it easier for breast cancer to spread to the lungs, according to a new mouse study. Researchers found these plastic particles attach to immune cells in the lungs and cause them to overload with sodium, swell up, and break down—triggering inflammation that helps cancer cells settle and grow. While this research was done in mice, not humans, it adds to growing evidence that everyday plastic pollution could pose real risks to our health, especially for people with cancer.
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.