Design Of Zeolite Imidazolate Skeleton Based Composite Nanomaterials And Study On Tumor Cell Therapy

Cancer is a serious disease affecting human health.In recent years,the treatment of cancer has been the focus of research.Among many treatment methods,the biological safety of traditional treatment methods such as surgery,radiotherapy and chemotherapy cannot be guaranteed,so it is often accompanied by problems such as poor treatment effect and large side effects.In order to overcome the limitations of traditional treatment methods,it is necessary to develop new treatment methods with low toxicity,high treatment efficiency and high targeting.With the development of nanotechnology,a new cancer treatment platform based on nanomaterials has been built.Among them,metal-organic frameworks have attracted wide attention of researchers in biomedical field because of their unique p H responsiveness,high specific surface area,high porosity and good biocompatibility.Based on this consideration,several zeolite imidazolate skeleton（ZIF）derivatives were designed and prepared in this paper,and their mechanism of action and therapeutic effect of cancer were explored.The main contents are as follows.（1）The ZIF-67 nanoparticles were prepared by nano coprecipitation method,and then the nanoparticles were stirred in the solution of ferric nitrate nine-hydrate,and a Fe-doped（Fe/ZIF-67）nanocomposite was prepared.Fe/ZIF-67 has the characteristics of p H response and glutathione（GSH）depletion,and it can be cracked to release Co²⁺and Fe³⁺in the weak acidic environment of cancer cells.On the one hand,Co²⁺can participate in the decomposition process of H₂O₂ and decompose H₂O₂ into toxic hydroxyl radical（·OH）.On the other hand,Fe³⁺can consume GSH which has a scavenging effect on·OH,thus improving the utilization rate of·OH.In addition,the resulting reduction product Fe²⁺can further undergo Fenton-like reactions to produce more·OH to kill cancer cells.Based on this principle,Fe/ZIF-67 has good targeting and enhanced chemical kinetics（CDT）therapeutic effect.（2）A Cu-doped ZIF-67（Cu/ZIF-67）nanocomposite was prepared by nano-coprecipitation method with cobalt nitrate hexahydrate,copper nitrate trihydrate and2-methylimidazole as raw materials.Subsequently,the anticancer drug 5-fluorouracil（5-FU）was loaded into it by solution impregnation method,and Cu/ZIF-67@5-FU with a size of about 500 nm was successfully synthesized.This material can catalyze the decomposition of H₂O₂ into OH in tumor cells to realize CDT.At the same time,the released Cu²⁺can consume GSH which can scavenge·OH to enhance the effect of CDT.In addition,the cleavage of Cu/ZIF-67@5-FU can release 5-FU for synchronous chemotherapy,thus realizing the synergistic treatment of CDT and chemotherapy.Cell experiments show that Cu/ZIF-67@5-FU has a good killing effect on cancer cells.（3）Zn-doped ZIF-67（Zn/ZIF-67@Mn O₂）nanocomposites coated with Mn O₂ were prepared using cobalt nitrate hexahydrate,zinc nitrate hexahydrate,2-methylimidazole and potassium manganese as raw materials.Among them,the Mn O₂ shell can consume GSH which can clear·OH and generate Mn²⁺.Zn/ZIF-67 can lyse to release Zn²⁺and Co²⁺in the acidic environment of cancer cells.Subsequently,Mn²⁺,Zn²⁺and Co²⁺catalyzed the decomposition of H₂O₂ into·OH,thus enhancing CDT treatment.The results of cell reactive oxygen species（ROS）tests demonstrated that Zn/ZIF-67@Mn O₂ produces large amounts of·OH and can cause cancer cell death even at low concentrations.