| With the emergence of people’s bad habits,the incidence of cancer is gradually increasing.How to effectively reduce the risk of cancer and treat cancer has become an urgent public health problem that needs to be addressed.Surgery,chemotherapy,and radiotherapy are the most traditional treatment methods.At this stage,they are still the most commonly used treatment methods in the first-line clinical cancer treatment.Among them,chemotherapy is the most common treatment.However,these treatment methods have some disadvantages,such as prone to spread of cancer cells,damage to normal cells,short half-life,low bioavailability,and high drug resistance.The use of nanocarriers with good Biocompatibility,high drug loading and targeted drug delivery capability can effectively improve the efficacy,toxicity and side effects of drugs.This subject has designed and developed a nano-drug carrier system based on metal organic framework material ZIF-90.The ZIF-90 material with a particle size of about 250 nm was prepared and used for the loading of anti-tumor drugs.It was characterized by scanning electron microscope(SEM),Fourier infrared spectroscopy(FT-IR),etc.Using the principle of Schiff base reaction,the target peptide RGD was modified on the surface of the material and characterized by FT-IR.Then,the anti-tumor drug paclitaxel(PTX)was loaded and its drug release ability was studied.The release of PTX from PBS buffer solution with pH=7.4 and pH=5.5 was investigated under different pH conditions.The results showed that under the condition of pH=5.5,the PTX release rate reached 90%.Finally,the three drug groups ZIF-90,PTX,and RGD/PTX@ZIF-90 were subjected to in vitro cell viability experiments and cell uptake experiments,respectively.The results show that ZIF-90 itself is not toxic to cells,while the RGD/PTX@ZIF-90 group is more toxic to cells than the PTX group.When the drug concentration in the RGD/PTX@ZIF-90 group and the PTX group was 400 μg/mL,the apoptosis rates of tumor cells in the two groups were 44.5%and 37.3%,which were consistent with the results of the cytotoxicity experiment.In addition,cell uptake experiments have proved that the composite material RGD/PTX@ZIF-90 can reach the tumor cells and have a therapeutic effect.Based on the improvement of tumor treatment effect after ZIF-90 loaded with PTX,a similar doxorubicin(DOX)drug delivery system was constructed.Using the principle of Schiff base reaction,DOX was modified on the surface of the material and characterized by FT-IR.Then,glucose oxidase(GOD)was loaded into the modified ZIF-90 material,and the glucose-consuming properties of GOD were used to obtain the nanocomposite drug-carrying system DOX/GOD@ZIF-90 with starvation treatment and chemotherapy effects.The drug release performance and tumor cell uptake capacity of DOX/GOD@ZIF-90 were studied separately.The experimental results show that the release amount of the drug in the pH=5.5 buffer is about 75%,and the release amount in the pH=7.4 buffer is only about 25%.In the in vitro activity experiment,DOX/GOD@ZIF90 can be taken up by tumor cells,and its lethality to tumor cells is higher than that of the DOX group alone.In mice in vivo experiments,the tumor size in mice treated with DOX/GOD@ZIF-90 was also significantly smaller than the DOX group alone,and the normal tissues and organs of the mice were not damaged.In this study,two kinds of nano-drug delivery systems were constructed and their antitumor activities in vitro and in vivo were analyzed.It was found that both the efficacy and side effects of the drug were significantly improved compared with those of the drug alone.Thus,the use of nano-materials to construct a composite drug delivery system can greatly improve the drug resistance,poor targeting and toxic side effects of single tumor drug therapy,and provide reference for the development of new anti-tumor drugs,it also provides a theoretical basis for the application of nano-materials in the field of medicine. |
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