MFP-FePt-GO Nanocomposites Promote Radiosensitivity Of Non-small Cell Lung Cancer Via Activating Mitochondrial-mediated Apoptosis And Impairing DNA Damage Repair

Background Recent advances in nanomedicine provided promising alternatives for tumor treatment to improve the survival and life quality of cancer patients.This study was designed to explore the insight mechanisms of the anti-tumor effects of the novel nanocomposites(NCs)MFP-Fe Pt-GO on non-small cell lung cancer(NSCLC).Methods A chemical co-reduction method was applied to the synthesis process of MFPFe Pt-GO NCs.The chemical synthesis efficiency and morphology of the NCs were measured with spectroscope and transmission electron microscope.Colony formation assay and cell apoptosis were conducted to assess the radiosensitivity effect of NCs with radiation.The mitochondrial membrane potential and reactive oxygen species(ROS)levels were detected by flow cytometry to further explore the cause of cell death.Immunofluorescence staining and confocal microscopy were performed to determine the DNA damage repair.A Lewis lung carcinoma animal model was used to measure safety and anti-tumor efficiency in vivo.Results The novel MFP-Fe Pt-GO NCs designed on a lamellar-structure magnetic graphene oxide and polyethylene glycol drug delivery system was synthesized and functionalized for co-delivery of metronidazole and 5-fluorouracil.While no severe allergies,liver and kidney damage,or drug-related deaths were observed,MFP-Fe PtGO NCs promoted radiosensitivity of NSCLC cells both in vivo and in vitro.It improved the effects of radiation via activating intrinsic mitochondrial-mediated apoptosis and impairing DNA damage repair.These NCs also induced a ROS burst,which suppressed the antioxidant protein expression and induced cell apoptosis.Furthermore,MFP-Fe Pt-GO NCs prevented NSCLC cell migration and invasion.Conclusion MFP-Fe Pt-GO NCs showed a synergistic anti-tumor effect with radiation to eliminate tumors.With good safety and efficacy,these novel NCs could be a potential radiosensitive agents for NSCLC patients.