FePt-Cys Nanoparticles Induce ROS-dependent Cell Toxicity,and Enhance Chemo-radiation Sensitivity Of NSCLC Cells In Vivo And In Vitro

Non-small cell lung cancer(NSCLC)was the highest mortality human malignancy over the past 30 years,and 60%are diagnosed at advanced stage.Chemoradiotherapy as a well-established treatment paradigm in oncology had obtain satisfactory effect compared to single treatment of chemotherapy and radiotherapy.But few agents have been identified to improve the therapeutic ratio and meet the requires of chemoradiotherapy.Recent years,the rapid development of nanomaterials has offered new strategies to improve chemoradiotherapy.FePt-Cys nanoparticles has brought about a significant impact for biomedical applications,due to their optimal magnetic1,optical properties and controllable morphology.In the present study,a chemical reduction method was applied to synthesize the nanoparticles(NPs)and FePt NPs were further modified with cysteamine(Cys)to improve the solubility and stability of water solutions.FePt-Cys NPs were characterized by means of transmission electron microscope(TEM),X-ray diffraction(XRD),fourier transform infrared spectroscopy(FTIR)and X-ray photo-electron spectroscopy(XPS).We explored the potential mechanisms of the antitumor effects of this new nanoparticle system in non-small cell lung cancer cell lines.In the in vitro study,FePt-Cys NPs induced a reactive oxygen species(ROS)drastic burst in H1975 and A549 cells,which suppressed the antioxidant protein expression and further induced cell apoptosis.Meanwhile,FePt-Cys NPs prevented the migration and invasion of NSCLC cells by downregulated MMP-2/9 expression and enhanced the cellular attachment.Furthermore,we demonstrated that FePt-Cys NPs promoted the effects of chemo-radiation through activation of the caspase system and impairment of DNA damage repair.In the in vivo study,no severe allergies or drugrelated deaths were observed and FePt-Cys NPs showed a synergistic effect with cisplatin and radiation.In conclusion,with good safety and efficacy,FePt-Cys NPs could therefore be potential sensitizers for chemoradiotherapy.