Metal-Organic Framework-loaded Enzymes For Tumor Photodynamic And Chemodynamic Therapy

Malignant tumors seriously threaten the life and health of human beings.Traditional treatment methods such as surgery and radiotherapy are limited affect their therapeutic effects due to side effects.In recent years,photodynamic therapy and chemodynamic therapy have attracted widespread attention in the field of biomedicine.The principle of action is to generate highly reactive and strongly oxidizing reactive oxygen species to induce apoptosis by damaging their organelles,proteins and DNA.However,the therapeutic effects are limited by the weak acidity and hypoxia in the tumor microenvironment.In this thesis,we constructed enzyme-metal-organic framework nanomaterials to improve tumor therapeutic efficacy by modulating the tumor environment with bioenzymes.1.We constructed a metal-organic framework Hf-Mn-TCPP-loaded glucose oxidase（GOx）for chemodynamic therapy of mouse breast cancer cells.GOx catalyzed the glucose to produce glucose acid and H₂O₂ in tumor,which not only reduced the p H in tumor cells and provided more suitable conditions for the Fenton-like reaction,but increasing the concentration of intracellular H₂O₂ effectively enhanced the effect of chemodynamic therapy.In vitro and in vivo experiments showed that the Hf-Mn-TCPP-GOx had good inhibition on mouse breast cancer cells.2.We constructed a metal-organic framework Mn-TCPP doped with rare earth ions Tb³⁺by ion exchange principle.Then lactate oxidase（LOX）was loaded on the basis of ionic ligand action for lactate-enhanced chemodynamic and photodynamic synergistic treatment of breast cancer.LOX catalyzed lactate to generation of H₂O₂and pyruvate,which enhanced the effect of chemodynamic therapy by increasing acidity and Fenton-like reaction substrates.Meanwhile,Mn³⁺reacted with H₂O₂ to produce Mn²⁺and O₂,thus alleviating tumor hypoxia and enhancing the effect of photodynamic therapy.Under 650 nm laser irradiation,LOX@Mn-TCPP（Tb）exhibited good photodynamic and chemodynamic therapeutic effects and was able to effectively induce apoptosis in breast cancer cells.