Prompt Description

Title: Surface Chemistry Orchestrates the Immunological Identities of Nanoplastics via Protein Corona Formation Scientific Question: How do the surface functional groups of nanoplastics (PS) exposed via the bloodstream specifically encode the protein corona formed in serum? How does this differentiated protein corona, generated by surface chemistry, determine the immun recognition patterns, cellular responses, and ultimate toxic effects of nanoparticles in mice? Methods: First, 200 nm polystyrene nanoparticles with carboxyl (PS-COOH), amino (PS-NH2), and unmodified (PS) surface modifications were selected and characterized. They were then incubated with mouse serum in vitro, and proteomic analysis was performed using liquid chromatography-tandem mass spectrometry to identify the differential expression of proteins in the three protein coronas. This comparison clarified the specific regulatory effects of surface functional groups on protein corona composition. Subsequently, a blood exposure model (tail vein injection) was established, and transcriptome sequencing was performed on mouse peripheral blood cells at the single-cell level. Differential expression gene analysis and KEGG pathway enrichment analysis were conducted on the sequencing data for each cell subpopulation to systematically map the immune cell-specific transcription profiles induced by nanoplastics with different protein coronas. Finally, using mouse macrophages as an in vitro model, bare particle groups and pre-coated protein corona particle groups were established. Cell viability was assessed using the CCK-8 method, cellular uptake efficiency was quantified by flow cytometry, and inflammatory cytokine levels were measured by ELISA. Spearman correlation analysis was performed to integrate protein corona composition data with cellular function data, establishing a quantitative relationship between key protein adsorption and biological effects, with the aim of revealing the complex interaction mechanisms between surface functional groups, protein adsorption, and immune responses. Conclusions: The study demonstrates that surface charge is a crucial factor in regulating protein corona composition. Carboxylation leads to the specific enrichment of complement and coagulation proteins, while amination primarily adsorbs apolipoproteins and albumin. This specific adsorption is not random but is driven by molecular properties such as surface potential and protein isoelectric point, achieving a precise conversion of surface chemical information into biological molecular identity. PS-COOH with a complement protein corona is efficiently recognized and endocytosed by macrophages through complement receptors and other pathways, specifically activating the NF-κB signaling axis and driving classical inflammatory pathways such as TNF and IL-17, triggering a strong immune response. In contrast, PS-NH2 with an apolipoprotein corona mimics endogenous lipoprotein particles, reducing rapid clearance by the endothelial phagocytic system, prolonging blood half-life, and primarily inducing upregulation of mitochondrial respiratory chain genes and disruption of oxidative phosphorylation pathways.