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Nanoplastics (NPs) are good carriers of persistent organic pollutants (POPs) such as polybrominated diphenyl ethers (PBDEs), and can alter their bioavailability and toxic impacts to aquatic organisms. This study highlights the single and combined toxic effects of polystyrene nanoplastics (PS-NPs) and 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47, one of the dominant congeners of PBDEs) on zebrafish embryos after an exposure duration of up to 120 hpf. Results showed that PS-NPs and BDE-47 co-exposure exacerbated the morphological deformities in terms of pericardial edema, yolk sac edema and curved tail in zebrafish larvae. Compared to BDE-47 single exposure, the combined exposure caused lower survival rates, shorter body lengths, and accelerated spontaneous movements. Further, PS-NPs were quickly aggregated on the surface of the embryonic chorions covered almost the entire membrane at 12 and 48 hpf, and concentration dependent accumulation was also found in the brain, mouth, trunk, gills, heart, liver and gastrointestinal tract at the larval stages. During the recovery period (7 days), PS-NPs were released from all the organs, with the highest elimination from the gastrointestinal tract. Histopathological examination revealed that co-exposure caused greater damage to retinal structures, muscle fibers and cartilage tissues. Responses of hypothalamic-pituitary-thyroid axis (CRH, TSHβ, NIS, TTR, Dio2, TG, TRα and TRβ) and reproduction (Esr2 and Vtg1) related genes were also investigated, and results showed that the co-exposure induced more significant upregulated expressions of TSHβ, TG, Doi 2, and TRβ, compared to BDE-47 single exposure. In conclusion, co-exposure to NPs and BDE-47 exacerbated developmental and thyroid toxicity in zebrafish, generally elucidating the toxicological effects mediated by complex chemical interactions between NPs with POPs in the freshwater environment. [Display omitted] • NPs with a diameter of 80 nm can be effectively blocked by the chorion of zebrafish embryos. • Toxicological effects of NPs and BED-47 on hypothalamus-pituitary-thyroid of zebrafish embryos. • Co-exposure of NPs and BED-47 caused serious damage to the retinal structure of zebrafish. [ABSTRACT FROM AUTHOR]