The Study Of Nitroxide Radical-ferroferric Oxide Hybrid Nanoparticles In The Diagnosis And Treatment Of Tumor Autophagy

With the increasing incidence of malignant tumors,malignant tumors are currently one of the biggest causes of human death.In the body,malignant tumors and normal tissue cells have different characteristics in the growth progression,such as autophagy.Autophagy not only provides the necessary energy and substrate supply for tumor growth and metastasis,but also is related to the improvement of tumor chemotherapy resistance.Therefore,it has become particularly important that how to effectively monitor the autophagy of tumors in the body and improve the effect of chemotherapy treatment by regulating the autophagy of tumorIn this study,autophagy in tumor cells has been studied by preparing nitroxide radical-ferroferric oxide(Fe₃O₄-NO·)hybrid nanoparticles.Then,according to the autophagy of tumor cells,anti-tumor treatment is carried out by regulating tumor autophagy and chemotherapeutic drugs.The specific work is as follows:(1)Firstly,an magnetic resonance imaging(MRI)contrast agent capable of monitoring tumor cell autophagy has been prepared.Fe₃O₄-NO·nanoparticles were synthesized by grafting dendrimers on the surface of Fe₃O₄nanoparticles and modifying nitroxide radicals(NO·)at the ends.Among them,nitroxide radicals and ferric oxide can be used to enhance T1 and T2 weighted MR imaging,respectively.Because the increase of autophagy level will be accompanied by the production of a large number of reactive oxygen free radicals(ROS),and nitroxide free radicals can be quenched by intracellular ROS,resulting in a decrease in the T1 signal generated by nitroxide free radicals;at the same time,Fe₃O₄is basically not subject to changes in the level of autophagy in cells,making T2 signals basically unchanged.In addition,we have also increased the number of nitroxide radicals on a single nanoparticle by grafting polymers on the surface of ferroferric oxide,avoiding the problem of low relaxation rate of single nitroxide radicals.In summary,we have successfully used Fe₃O₄-NO·nanoparticles to monitor autophagy in tumor cells.(2)Autophagy inhibitor 3-methyladenine(3-MA)and autophagy inducer rapamycin(Rapa)have been used to chemically induce or inhibit autophagy in tumor tissue cells.And,ROS detection and magnetic resonance imaging(MRI)were used to determine the working concentration of 3-MA and rapamycin.Then,in the working concentration of 3-MA and rapamycin,combined with the chemotherapy drug doxorubicin hydrochloride(Dox)for in vitro anti-tumor treatment.Finally,we treated tumor-bearing mice with different treatment options(autophagy regulation+Dox),and we found that the combination of 3-MA and Dox has the best effect.Therefore,we can conclude that the autophagy inhibitor 3-MA inhibits the autophagy behavior of tumor cells and hinders the way that autophagy provides energy and response substrates for tumor cells.3-MA weakens the stress ability of tumor cells,so that chemotherapy achieves a better therapeutic effect.