Study On Application Of A Multifunctional Nanoparticles Combined With Microwave Therapy And Chemotherapy In Tumor Treatment

The burden of cancer incidence and global mortality is increasing rapidly.In 2020,there were 19.3 million new cancer cases and nearly 10 million new cancer deaths in the world.It is estimated that by 2040,the global cancer burden will reach 28.4 million cases,an increase of 47%over 2020.Providing cancer treatment and care is very important for global cancer control.Microwave dynamic therapy is a new tumor dynamic therapy,which has the advantages of low cost,non-invasive and wide applicability.The principle of microwave dynamic therapy is that microwave sensitizer enriched in tumor is irradiated by microwave to produce active oxygen,thus killing tumor.In this paper,an open framework nanoparticle(MCOF-3)based on cluster-based metal-chalcogenide open frameworks was synthesized by hydrothermal-solvothermal method.The biocompatibility of APA@MCOF-3@MnO₂@PEG was improved by coating MnO₂ shell on its surface,then loading Apatinib.MCOF-3@MnO₂@PEG nanoparticles were finally applied in the treatment of tumor combined with microwave dynamic therapy,microwave hyperthermia and chemotherapy.The morphology and elemental composition of MCOF-3@MnO₂@PEG nanoparticles were analyzed by scanning electron microscope and transmission electron microscope.The hydrated particle size of MCOF-3@MnO₂@PEG nanoparticles were measured by Zeta potential particle size analyzer.The parameter changes of these nanocomposites before and after coating and modification were characterized by Fourier transform infrared spectrometer,Zeta potential and hydrated particle size changes,and the coating conditions were analyzed and determined.The successful preparation of APA@MCOF-3@MnO₂@PEG was indicated by the above series of characterization.The drug loading rate was characterized by UV spectrophotometer.The results showed that the drug loading rate of MCOF-3was significantly increased after being coated with MnO₂ shell.The specific surface area and porosity analyzer test showed that the specific surface area of the material was significantly increased after being coated with MnO₂ shell,which was the main reason for the increase of drug loading capacity.We found that microwave irradiation of MCOF-3 nanoparticles can make it produce reactive oxygen species,which has good microwave dynamic sensitization.However,in the process of tumor growth,cancer cell reproduction usually exceeds its blood vessel supply,coupled with functional defects and frequent coagulation of proliferative tumor blood vessels,resulting in the formation of hypoxia and necrotic areas,which usually have significantly lower oxygen tension than the surrounding normal tissues.The lack of oxygen in tumor microenvironment can be improved by coating MCOF-3 with MnO₂ shell as a self-oxygen supply system,which can generate oxygen during microwave dynamic therapy by catalyzing excessive H₂O₂ in tumor microenvironment,thus enhancing the therapeutic effect on tumor.The evaluation of biological safety of MCOF-3@MnO₂@PEG nanoparticles was completed by acute toxicity experiments in cells and mice.The experimental results showed that MCOF-3@MnO₂@PEG nanoparticles had low toxicity and good biocompatibility,and the maximum concentration of MCOF-3@MnO₂@PEG nanoparticles was 200?g/m L,which had low biological toxicity to Hep G-2,L929 and H22 cells.In the acute toxicity experiment,we selected three concentrations(50 mg/kg,75 mg/kg and 100mg/kg)to investigate the biological toxicity of MCOF-3@MnO₂@PEG to mice.The results showed that the growth curve was good and there was no death in mice,and.Histological analysis showed that there was no damage or lesion in mice tissues.We also explored the microwave sensitivity enhancement performance of MCOF-3@MnO₂@PEG nanoparticles.After 5 minites of microwave irradiation,the temperature of saline with 7.5 mg/m L MCOF-3@MnO₂@PEG nanoparticles increased by 32.4?,which was significantly higher than that of normal saline control group,indicating that it has good microwave hyperthermia sensitivity enhancement performance.In addition,in order to further study the microwave hyperthermia sensitivity enhancement performance of nanoparticles,we tested that the reactive oxygen species types that MCOF-3@MnO₂@PEG can produce are hydroxyl radicals and singlet oxygen,and the microwave dynamic performance of MCOF-3@MnO₂@PEG is significantly improved in the presence of H₂O₂.The final treatment results of mice showed that the tumor inhibition rate of APA/MCOF-3@MnO₂@PEG nanoparticles was 79.8%.In this paper,a new sensitizer(MCOF-3@MnO₂@PEG)for microwave hyperthermia and microwave dynamic therapy was developed,and its sensitizing performance was explored through a series of experiments.It can realize self-oxygen supply in the process of microwave dynamic therapy,and finally it was applied to the combined treatment of tumor with microwave dynamic therapy,microwave hyperthermia and chemotherapy,and finally achieved good therapeutic effect in animal experiments,providing ideas for developing new microwave sensitizers.