Preliminary investigation on cytotoxicity of fluorinated polymer nanoparticles

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（PTFEPMMA 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 5.0 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/m L） 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.

Synthesis of fluorinated CaCO_(3)-based oxygen-supplying nanophotosensitizers to potentiate photodynamic immunotherapy by reversing tumor hypoxia and immunosuppression

Photodynamic therapy is a noninvasive type of phototherapy with a high capacity to boost specific antitumor immunity by causing immunogenic cell death.However,the photodynamic therapeutic potency toward solid tumors is dampened by tumor hypoxia that negatively impairs the generation of cytotoxic singlet oxygen and promotes the formation of tumor immunosuppression.Herein,fluorinated CaCO_(3)(CaF)nanoparticles are prepared with the addition of dopamine-conjugated perfluorosebacic acid and ferric chloride into a calcium chloride ethanol solution via an ammonium bicarbonate-mediated gas-diffusion process.After being coated with commercial lipids and hexadecylamin conjugated chlorin e6(hCe6)via a templated self-assembly process,the yielded PEGylated nanophotosensitizer(hCe6@CaF-PEG)exhibits an effective loading efficiency to perfluoro-15-crown-5-ether(PFCE),a model perfluorocarbon molecule,and thus oxygen molecules.Upon intravenous administration,the obtained PFCE/hCe6@CaF-PEG can alleviate tumor hypoxia by working as an oxygen nanoshuttle.Together with local light emitting diode light exposure,photodynamic treatment with PFCE/hCe6@CaF-PEG can suppress the growth of primary CT26 tumors and unirradiated distant tumors,particularly when synergized with anti-PD-1(aPD-1)immunotherapy to collectively reverse tumor immunosuppression.This work presents an effective strategy to potentiate photodynamic immunotherapy by concurrently reversing tumor hypoxia and immunosuppression.