Preparation Of CZTS@COF@L-arg@5-FU Nanomaterials And The Therapeutic Effect On Liver Cancer Of Mice

Objective: The purpose of this study was to investigate the therapeutic effect of synthetic CZTS@COF composite nanomaterials loaded with L-arg and 5-FU on liver cancer cells and liver cancer models,and to analyze its possible mechanism.Research methods: In this experiment,CZTS nanocrystals were synthesized by water bath reflux and oil bath at 180℃ under nitrogen environment,and COF materials were coated in layers to obtain CZTS@COF nanomaterials,which were characterized in different ways,such as scanning electron microscopy,transmission electron microscopy,etc.In addition,experiments on L929 mouse epithelioid fibroblasts and H22 mouse hepatocellular carcinoma cells proved that the material had good biosafety,and had an inhibitory effect on hepatocellular carcinoma cells.At the same time,the drug loading ability,microwave dynamic performance and NO release ability of the material were measured.Result: We successfully synthesized CZTS@COF material,whose potential is-14.3mv and particle size is about 295 nm.After analyzing its elements,it was found that the weight percentage of copper in the material reached 35.07%.It was found through calculation that the drug loading rate of CZTS@COF material for 5-FU reached 31.8%,which had good drug loading capacity,and had good microwave dynamic catalytic effect under microwave conditions,and could produce a large number of ROS.Under the condition of carrying L-arg,NO can be catalyzed to produce micromolar level concentration.CZTS@COF showed good cytocompatibility to both L929 and H22 cells,and the cell activity was still above 90% when the concentration was 200μg/ml.The activity of H22 cells decreased to 36.81% after microwave-assisted treatment with L-arg and 5-FU.At the same time,the results of fluorescence microscopy showed that CZTS@COF could produce a large number of ROS under single application or microwave catalysis,and reagent tests after cell lysis showed that CZTS@COF@Larg@5-FU could produce more than 4μM of NO in cells,thus exerting the effect of tumor inhibition.In animal experiments,CZTS@COF showed good biological safety,and no abnormalities were found in body weight,blood biochemistry and blood routine of mice.In the experimental treatment of tumor-bearing mice,microwave therapy alone only showed a slight tumor inhibition effect,and the tumor growth did not decrease significantly,but grew rapidly to the level close to the control group in the later stage.In contrast,after CZTS@COF@L-arg@5-FU and microwave therapy,the tumor growth was significantly inhibited.Compared with the control group,the inhibitory rate was79.1%,showing a more obvious therapeutic effect.Conclusion: We have designed a new nanomaterial which can realize the combination therapy for tumor and provide a new idea for the treatment of liver cancer.