Metal-Organic Frameworks Immobilized Enzyme And Applications In Cancer Therapy

Cancer is one of the most major diseases that threatens human health and life.At present,biological enzymes have been widely applied in tumor therapy fields.However,low thermostability,narrow pH range and the weak endurance to environment hindered its practical applications.In this article,nanoscale metal-organic framework was used to immobilize biological enzyme.The catalytic performance and the chemodynamic therapy and photodynamic therapy of tumors were studied detailedly.Specific work of this article are as follows:(1)Nanoscale metal-organic framework(Hf-DBA)was synthesized and used to immobilizate the horseradish peroxidase(HRP).The structures of Hf-DBA were characterized by TEM,UV-vis,Fluorescence spectrophotometry,XRD,Nitrogen adsorption-desorption,etc.The results showed that the immobilization rate of 11.35%for HRP.HRP@Hf-DBA exhibited good stability and higher catalytic activity than that of HRP under different pH and temperature.HRP is a glycoprotein,formed by the combination of colorless enzyme protein and brown iron porphyrin.The active center iron porphyrin can react with H₂O₂ overexpressed in tumor cells to produce reactive oxygen species to induce tumor cell apoptosis.Cytotoxici ty test and cell imaging analysis demonstrated that HRP@Hf-DBA presented excellent chemodynamic therapy effect on Hela cells and A549 cells.(2)Nanoscale Mn-porphyrin MOF(Mn-TCPP)was synthesized and used to immobilize glucose oxidase(GOx).The structures of Mn-TCPP were characterized by TEM,UV-vis,AFM Fluorescence spectrophotometry,XRD,Nitrogen adsorption-desorption,etc.The results showed that the immobilization rate of 11.75%for GOx from BCA protein assay kit.GOx can react with intracellular glucose to produce H₂O₂.Mn-TCPP can catalyze H₂O₂ to produce oxygen,which enhance therapeutic effect of photodynamic therapy by 650 nm laser irradiation.Mn-TCPP can consume glutathione and produce Mn²⁺and so the fenton-like reaction occur.The in vivo/in vitro experiments showed that GOx@Mn-TCPP could effectively induce A549cell and 4T1 cell apoptosis.Therefore,collaborative treatment of synergistic starvation therapy,photodynamic therapy and chemodynamic were realized by Mn-TCPP.