Design And Preparation Of MOF-based Nanoprobes And Their Application For Tumor Starvation Therapy

Malignant tumors(cancers)have become one of the major diseases affecting human health.However,currently available cancer treatment methods suffer from many shortcomings,which seriously limited the cure rate of cancer.Therefore,the development of reasonable methods to effectively treat cancer is the focus of current scientific and clinical researches.Glucose oxidase(GOx)-mediated tumor starvation therapy has become a promising tumor treatment strategy.However,the poor stability of GOx makes it difficult to achieve efficient in vivo delivery,the welldeveloped internal defense system in tumor cells also greatly limits the application of GOx.Therefore,effective methods are of great significance for enhancing the efficiency of GOx tumor treatment.Metal-organic frameworks(MOFs)are a new class of crystalline porous materials with good designability,modification,and biocompatibility,and are widely recognized in nanomedicine.The latest research shows that MOFs can effectively stabilize the protein structure and prevent its deformation in many harsh environments,thereby greatly expanding the application range of proteins such as enzymes.In this paper,two nanoprobes(nanoreactors)were developed based on nano-MOF,GOx,photothermal reagent indocyanine green(ICG),autophagy inhibitor chloroquine,and homologous cancer cell membrane to enhance the heating efficiency of GOx.Specifically includes the following two aspects of work: 1.Based on biomimetic biomineralization,GOx and photothermal agent ICG were effectively loaded into MOF,the probe was further obtained by surface modification of homologous cancer cell membrane.Thanks to the nanoconfinement effect of MOF,the nanoprobe can effectively maintain the enzymatic activity of GOx in digest environment and high temperature.After entering cancer cells,the nanoprobe can effectively inhibit the expression of intracellular defensive proteins through the synergistic starvation-photothermal effect,which leads to the accumulation of toxic substances in the cells and eventually induces tumor ablation.A series of experiments have proved the effectiveness and prospect of the probe.2.A nanoprobe that co-loading an autophagy inhibitor chloroquine and GOx was designed and synthesized.The synthesis of the probe was facile and controllable.Chloroquine can prohibit protective autophagy and damage the cell's defense system.Preliminary studies have shown that synergistic autophagy inhibition with starvation therapy has a good cell killing effect and the probe has a good prospect for tumor treatment.This probe is expected to further provide new ideas for the biomedical application of GOx.