| Objectives:Oral squamous cell carcinoma(OSCC)is a malignant tumor occurring in oral tissues,which poses a serious threat to human health.Hesperidin(HES)is an important flavonoid in the young fruit of Rutaceae,which is derived from natural plants.Hesperidin has high pharmacological activity and plays a prominent role in cancer treatment.However,due to its high hydrophobicity and low bioavailability,its inability to be systematically administered has limited its experimental studies in vivo.Zeolitic imidazolate framework material(ZIFs)is a kind of Metal-Organic Frameworks(MOFs)structure connected by zinc and imidazoles,which has good biocompatibility and pH sensitivity.It is an ideal drug carrier.In order to increase the bioavailability of hesperidin and the targeting of the drug at the tumor site,a pH-responsive drug delivery material was used in this study to reduce the toxic effect of the drug on normal cells and improve the targeted release of the drug.Methods:1.HES nanoparticles were prepared by mixing hesperidin and imidazole.Then hesperidin,imidazole and zinc acetate were mixed to synthesize HES@ZIF-zni nanoparticles through metal coordination.2.(1)The morphology of ZIF-zni and HES@ZIF-zni nanoparticles was observed by scanning electron microscopy(SEM)and transmission electron microscopy(TEM).(2)The particle size and Zeta potential of ZIF-zni and HES@ZIF-zni nanoparticles were analyzed by dynamic light scattering(DLS).(3)The morphology of ZIF-zni and HES@ZIF-zni nanoparticles was analyzed by X-ray diffraction(XRD).(4)Fourier Infrared transform spectroscopy(FT-IR)was used to analyze the characteristic absorption peaks.(5)The specific surface area(BET)and average pore size of ZIF-zni and HES@ZIF-zni nanoparticles were analyzed in nitrogen adsorption desorption experiments.3.In the cell experiment,CCK-8 results showed that the cell viability was significantly decreased and the killing effect was significantly enhanced when the concentration of HES@ZIF-zni nanoparticles was 40 μg/m L.The toxicity of HES@ZIF-zni nanoparticles was higher than that of HES and ZIF-zni.In addition,the survival rate of CAL-27 cells treated with ZIF-zni nanoparticles,which were not loaded with HES,was significantly higher than that of HES@ZIF-zni nanoparticles.In the experiment of cell death staining,obvious red fluorescence was found in both HES and HES@ZIF-zni nanoparticles,and the red fluorescence was more obvious in HES@ZIF-zni nanoparticles than in HES group.In the experiment of reactive oxygen species,obvious green fluorescence was observed in the HES@ZIF-zni group,and the fluorescence intensity of the HES@ZIF-zni group was significantly higher than that of the HES group.Results:1.ZIF-zni nanocarriers and HES@ZIF-zni nanoparticles were successfully prepared.2.SEM and TEM results showed that the average particle size of ZIF-zni nanocarriers was about 800 nm,and the particle size of HES@ZIF-zni nanoparticles did not change after HES loading,indicating that the morphology of HES@ZIF-zni nanoparticles was not affected during the synthesis process.The Zeta potential results show that there is little difference between the two potentials.The particle size measured by DLS is consistent with SEM and TEM.XRD results showed that HES did not affect the crystal structure of ZIF-zni nanocarriers during loading.In the FT-IR results,the HES characteristic peaks are masked because HES are loaded into HES@ZIF-zni.BET and aperture analysis further indicated that HES was successfully loaded into HES@ZIF-zni.3.In cell experiments,CCK-8 results showed that cell viability was significantly decreased and killing effect was significantly enhanced when the concentration of HES@ZIF-zni nanoparticles was 40 μg/m L.The toxicity of HES@ZIF-zni nanoparticles was higher than that of HES and ZIF-zni.In addition,the survival rate of CAL-27 cells treated with ZIF-zni nanoparticles,which were not loaded with HES,was significantly higher than that of HES@ZIF-zni nanoparticles.In the experiment of cell death staining,obvious red fluorescence was found in both HES and HES@ZIF-zni nanoparticles,and the red fluorescence was more obvious in HES@ZIF-zni nanoparticles than in HES group.In the experiment of reactive oxygen species,the green fluorescence was weaker in the HES@ZIF-zni group.Conclusion:1.ZIF-zni nanoparticles with pH response performance were successfully prepared,and the nanoparticles had good cell targeting.2.A series of characterization of ZIF-zni and HES@ZIF-zni nanoparticles proved that HES was successfully loaded on ZIF-zni nanoparticles without affecting the crystal structure.3.Cell experiments have proved that HES@ZIF-zni nanoparticle set has high toxicity to CAL-27 cells,and that it has good killing effect on tumor cells through generating reactive oxygen species.Moreover,ZIF-zni nanoparticles have low toxicity. |
