Inflammatory Microenvironment Reshapes the Protein Corona of Polystyrene Nanoplastics to Exacerbate Periodontitis Progression

Nanoplastics (NPs) are emerging environmental pollutants with widespread human exposure and potential health risks. Once entering biological systems, NPs readily acquire a protein corona (PC) that governs their biological identity and toxicity. However, how disease-associated microenvironments reshape PC and modulate NPs toxicity remains poorly understood. Here, we investigated the effects of the oral inflammatory microenvironment on PC and the biological behavior of polystyrene (PS) NPs using periodontitis as a model disease. We identified a disease-specific PC formed in the saliva of periodontitis patients, characterized by enrichment of apolipoproteins, complement, and coagulation proteins. Compared with the normal PC, this disease-specific PC markedly enhanced macrophage uptake of PS NPs via increased phagocytosis and lipid raft/caveolin-mediated endocytosis, and triggered stronger pro-inflammatory responses, including elevated reactive oxygen species production, M1 macrophage polarization, and cytokine secretion. In vivo, oral exposure to PS NPs exacerbated alveolar bone loss and inflammation in a periodontitis mouse, accompanied by enhanced macrophage M1 polarization and systemic inflammatory responses. Mechanistically, these effects were closely associated with the complement-enriched disease-specific PC that amplified NPs-immune cell interactions. Overall, this study demonstrates that inflammatory microenvironments can reshape the PC of NPs and intensify their toxicological outcomes, underscoring the need for health-dependent risk assessment of NPs.