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As well-known persistent organic pollutants (POPs),organofluorine pollutants such as perfluorooctane sulfonate (PFOS) have been proven to be bioaccumulated and harmful to health.However,toxicological assessment of organofluorinated nanoparticles,which have emerged as a novel tool for biomedical and industrial applications,is lacking,to the best of our knowledge.To assess the biological effects and health risk of fluorinated nanoparticles,trifluoroethyl aryl ether-based fluorinated poly(methyl methacrylate) nanoparticles (PTFE-PMMA NPs) were synthesized with various fluorine contents (PTFE-PMMA-1 NPs 12.0 wt.％,PTFE-PMMA-2 NPs 6.1 wt.％ and PTFE-PMMA-3 NPs S.0 wt.％),and their cytotoxicity was investigated in this study.The in vitro experimental results indicated that the cytotoxicity of PTFE-PMMA NPs was mild,and was closely related to their fluorine (F) contents and Fcontaining side chains.Specifically,the cytotoxicity of PTFE-PMMA NPs decreased with increasing F content and F-containing side chains.After exposure to PTFE-PMMA NPs at a sublethal dose (50 μg/mL) for 24 hr,the phospholipid bilayer was damaged,accompanied by increasing permeability of the cell membrane.Meanwhile,the intracellular accumulation of reactive oxygen species (ROS) occurred,resulting in the increase of DNA damage,cell cycle arrest and cell death.Overall,the PTFE-PMMA NPs were found to be relatively safe compared with typical engineered nanomaterials (ENMs),such as silver nanoparticles and graphene oxide,for biomedical and industrial applications.