Glucose Oxidase-based Nanoprobes For Cancer Diagnosis And Treatment

In recent years,glucose oxidase(GOx)-based nanoprobes have attracted widespread attention in the field of cancer diagnosis and treatment.GOx is an aerobic dehydrogenase widely found in nature,mainly derived from mold and honey.It can react with glucose and oxygen(O2)to produce hydrogen peroxide(H2O2)and gluconic acid.As a key source of nutrition supply for cells,glucose plays a vital role in tumor growth.Using the highly efficient catalysis reaction of GOx to glucose,the content of glucose can be measured by measuring the consumption of O2 or the output of H2O2 in the catalytic reaction,and the development of cancer also can be inferred.Therefore,the design of GOx-based glucose-specific probes for glucose detection in different tumor cells has important research value.In addition,the GOx catalytic reaction can specifically consumes glucose,which can cut off the nutritional source of cancer cells for starvation therapy.The H2O2 produced can enhance the oxidative stress of tumor tissues and further enhance the therapeutic effect at the same time.However,tumors have high complexity,diversity,and heterogeneity,so it is difficult to achieve the desired curative effect with a single starvation treatment.Therefore,the development of GOx-based nanoprobes for the synergistic therapy of tumors has important research value.In this thesis,two kinds of nanoprobes were designed by using the catalysis capability of GOx to glucose for the detection of intracellular glucose and the research of in vivo synergistic therapy of tumors.The main contents are as follows:(1)GOx covalently conjugated silver nanoparticles(Ag NC)were designed and prepared,and the enzymatic cascade reaction was used for the fluorescence detection of glucose in tumor cells.H2O2 is mainly produced by GOx catalyzed glucose oxidation.H2O2 can oxidize Ag NC to Ag ions,and Ag ions significantly enhanced the red fluorescence signal of the silver ion probe(Ag~+-FP)to achieve the effect of amplification of the fluorescence signal,and effectively improve the sensitivity of glucose detection.In summary,this section designs a sensitive and specific cascade response for intracellular glucose detection,which opens up a new avenue for intracellular glucose detection.(2)A nanoprobe(SRF@GOx)loaded with sorafenib(SRF)was designed and prepared,which was successfully used for the starvation-ferroptosis synergistic cancer therapy.In specific,the hydrophilic protein(GOx)can be induced by hydrophobic small molecule(sorafenib)to assemble into nanoparticles(SRF@GOx)with a particle size of about 150 nm due to the hydrophobic interaction.The nanoparticles could reduce the toxicity of GOx in the blood circulation,extend its blood circulation time,and efficiently enrich to the tumor site through passive targeting.Subsequently,the nanoparticles dissociate at the tumor site and release SRF to induce ferroptosis in tumor cells.At the same time,GOx could consume tumor glucose,thereby achieving a starvation-ferroptosis synergistic cancer therapy.In summary,this study constructed two new GOx-based nanoprobes,which achieved tumor glucose detection and starvation-ferroptosis synergistic cancer therapy.This study provides new approaches for the development of GOx-based nanomaterials for cancer diagnosis and treatment,and have potential application prospects.