Study On Synthesis And Application Of MOF-199 And ZIF-90 With Tumor Microenvironment Response

The high incidence rate and high mortality rate of cancer threaten human life and health.According to statistics,in the past few decades,an estimated 14 million patients worldwide were diagnosed with cancer each year.With the development of science and technology,many new therapeutic schemes have been developed gradually,such as dynamic therapy,photothermotherapy,microwave hyperthermia and so on.Tumor microenvironment(TEM),as a special marker different from normal cells,is closely related to the proliferation,growth and metastasis of tumors.The development of medical nano materials with tumor microenvironment response and its application in these emerging therapeutic methods has become one of the research hotspots.There are many kinds of nano materials for tumor microenvironment response,such as liposomes,polymer,inorganic materials,metal organic nano materials and so on.Among them,metal organic frameworks(MOFs)are commonly used as drug carriers for tumor therapy due to their porous structure and modifiability.Especially,MOFs with tumor microenvironment response have expanded their applications.Therefore,it is important to design and prepare TME responsive MOFs for cancer diagnosis and treatment significance.In this paper,two kinds of MOFs,MOF-199 and ZIF-90,were synthesized by one-step method.TEM,SEM,XRD and FT-IR were used to determine the morphology,particle size and chemical structure of the material.And the main work and achievements are as follows:(1)The experimental synthesis of MOF-199 has a regular octahedral structure and excellent performance.It was found that MOF-199 has a variety of tumor microenvironment response ability.Firstly,MOF-199 is sensitive to ATP and GSH,which makes the material gradually degrade under the tumor microenvironment concentration,which helps to target tumor cells and slow and controlled drug release.Secondly,MOF-199 can catalyze H₂O₂ in tumor environment to produce hydroxyl radicals,which can directly kill cancer cells in dynamic therapy.At the same time,dissolved oxygen test found that MOF-199 has its own oxygen production capacity,which can largely solve the problem of lack of oxygen in the dynamic therapy of tumor.MOF-199 also has the ability of drug loading and surface modification,and combines glycolysis inhibitor shiokarin(SK)and bovine serum protein to obtain MOF-199@SK and MOF-199@BSA.In particular,MOF-199 also showed the ability to inhibit PKM2 in subsequent glycolysis inhibition experiments,which can be applied to tumor starvation therapy and reduce ATP energy supply.Microwave heating is also a major characteristic of MOF-199,which makes the application of MOF-199 more promising.Therefore,this study provides important data support for the follow-up application of MOF-199 in tumor therapy.(2)The experimental synthesis of ZIF-90 is a dodecahedron structure,and also has a variety of tumor microenvironment response ability.ZIF-90 can be biodegraded under the condition of tumor acidity(p H=5.5).Meanwhile,ZIF-90 is sensitive to ATP and GSH in tumor microenvironment,which makes ZIF-90 have multiple microenvironment response ability,which provides conditions for tumor therapy targeting and drug sustained and controlled release,and increases the utilization of materials.In the experiment,ZIF-90 could be loaded with apigenin(AP),a glycolysis inhibitor,on the basis of doxorubicin.ZIF-90could be used as a combination of chemotherapy and starvation therapy.In vitro experiments showed that ZIF-90,ZIF-90@AP and ZIF-90@AP@DOX all showed strong ability to inhibit PKM2.In conclusion,ZIF-90 is an excellent tumor microenvironment responsive nanomaterial.