Nanoplastics reshape local intracellular RNP environments and P-body dynamics

Nanoplastics are biologically active environmental particles, yet how they perturb intracellular organization before overt toxicity remains poorly understood. Here we show that nanoplastic exposure generates spatially restricted RNA–protein states that are largely obscured by whole-cell measurements. Polystyrene and polyethylene terephthalate nanoplastics induced cellular phenotypes distinct from canonical mitochondrial perturbations. Polystyrene-rich cytoplasmic regions were enriched in RNA-binding and P-body-associated proteins, together with transcripts involved in RNA processing and ribonucleoprotein organization, whereas whole-cell transcriptomics predominantly revealed broader stress-response programs. This local molecular reorganization was accompanied by time-dependent remodeling of DDX6-positive P-bodies in intestinal and respiratory epithelial cells. Recurrent motifs within locally enriched transcripts guided the design of RNA oligonucleotides that attenuated nanoplastic-associated P-body remodeling and improved cell viability. These findings identify spatial RNA–protein reorganization as an early feature of the intracellular nanoplastic response and show that locally enriched RNA sequence information can be harnessed to modulate particle-associated cellular dysfunction.