Synergistic Promotion of Triple‐Negative Breast Cancer Tumorigenesis and Metastasis by Oral Polystyrene Nanoplastics Exposure via Alloprevotella ‐Derived Glutamate and Platelet Activation

Abstract Nanoplastics (NPs) are emerging environmental pollutants with potential health risks, yet their role in cancer progression remains poorly understood. Here, this is demonstrated that oral exposure to 100 nm polystyrene nanoplastics (PS‐NPs) accelerates tumor initiation and metastasis in a murine triple‐negative breast cancer (TNBC) model, without affecting primary tumor growth. PS‐NPs do not directly alter TNBC cell behavior in vitro but induced gut microbiota dysbiosis, characterized by Alloprevotella enrichment and elevated systemic glutamate levels, both identified as key mediators of PS‐NPs‐driven tumor promotion. Moreover, PS‐NPs enhanced platelet activation, evidenced by increased aggregation, microthrombus formation at metastatic sites, and upregulation of CD36 and Serpine1. Collectively, these findings uncover a synergistic mechanism whereby oral PS‐NPs promote TNBC progression via a gut microbiota‐derived metabolite‐platelet axis, establishing an unrecognized link between environmental nanoplastic exposure and cancer progression, and highlighting potential therapeutic targets for intervention.