| The hypoxia of tumor cells significantly inhibits the therapeutic effect of radiotherapy and chemotherapy.Using the new technology in the field of nanotechnology,a hypoxic drug delivery system was designed and synthesised in the study,carrying chemotherapy drugs and radiosensitizers to improve the efficiency of tumor therapy.Specially,the MGO/FU-MI nanocomposites(NCs)with an average size of 245 nm,were synthesised step-by-step using EDC chemistry.Moreove,transmission electron microscopy(TEM)and dynamic light scattering device(DLS)were used to characterize its morphology and size.X-ray photoelectron spectroscopy(XPS)and energy distribution spectroscopy(EDS)were utilized to explore its chemical composition.Its chemical structure and drug loading and release characteristics were characterized by Fourier transform infrared spectroscopy(FTIR)and UV-VIS spectrophotometer.After determining its physical properties,MTT assay was conducted to detect its cytotoxicity and hypoxia sensitivity in vitro,while its toxicity mechanism was explored through cell cycle and intracellular reactive oxygen species(ROS)detection.In addition,the radiotherapy sensitization effect of it was detected by clonogenic survival analysis with 6MV X-rays.The study found that MGO/FU-MI NCs can affect DNA synthesis leading to S phase cell arrest,and stimulate the intracellular ROS augment,showing significant inhibition of cell proliferation.In addition,in terms of radiotherapy,MGO/FU-MI NCs are not only able to improve the efficiency of radiation but also enhance the radiosensitivity of cells which is an ideal radiosensitizer.Furthermore,we have found that metronidazole(MI)combined with 5-Fluorouracil(5-FU)has a drug-enhancing effect,and perfroming a self-amplifying sensitizing effect in both chemotherapy and radiotherapy.These experimental results indicate that MGO/FU-MI NCs are expected to be a potential chemotherapeutic sensitizer for future clinical studies. |
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