Study On Regulation Of Tumor Microenvironment And Efficiency Of Radiotherapy Based On Graphene-Mno₂ Complex

Cancer is one of the major diseases that threaten human life and health today,and the incidence rate is increasing year by year.Current treatments for cancer include surgical resection,chemotherapy and radiotherapy.However,each treatment method has its limitations.For example,surgery is often difficult to remove metastatic cancer cells.Chemotherapy and radiation therapy,however,are highly selective against normal cells and cancer cells because of their lack of specific selectivity.Effects,and due to the presence of tumor microenvironment in the presence of oxygen,induce cancer cells to produce drug resistance,and seriously affect the radiotherapy effect of the tumor.Functionalized nanographene,due to its special physicochemical properties,has shown great potential in the field of biomedicine,especially in the treatment and diagnosis of cancer.It is of far-reaching significance to develop a strategy based on functionalized graphene nanomaterials for improving the hypoxic microenvironment of tumors from improving the effect of radiotherapy.In this paper,graphene oxide?GO?was prepared from the graphite powder using the modified Hummers method.Using a large number of oxygen-containing groups on the surface,the MB?borane morpholine complex?and potassium permanganate were combined.The rGO-MnO₂ nanocomposite was prepared and non-covalently modified on the surface by C18PMH-PEG?PEG-grafted polymaleamide complex?to obtain rGO-MnO₂-PEG nanomaterial.The GO,rGO-MnO₂ and rGO-MnO₂-PEG nanocomposites were characterized by transmission electron microscope,ultraviolet-visible spectrophotometer and atomic force microscope.By simulating the hypoxic tumor microenvironment in vitro and the content of hydrogen peroxide,the catalytic properties of rGO-MnO₂-PEG nanomaterials were explored,and the MR imaging effect was also evaluated.Using 131I-labeled rGO-MnO₂-PEG nanomaterials,a diagnostic set was constructed.With the treatment of one-in-one nano drug delivery system,used for bimodal imaging?MR imaging and radionuclide imaging?under the guidance of mouse tumor radiotherapy.It was found that the rGO-MnO₂ nanocomposite has good stability in different physiological solutions after being modified by C18PMH-PEG.The average hydrated particle diameters of rGO-MnO₂-PEG nanomaterials and rGO-MnO₂ were 24 nm and 80 nm,respectively.The former had better dispersibility than the latter.The rGO-MnO₂-PEG nanomaterial can catalyze the generation of oxygen in 100 ?M hydrogen peroxide solution in vitro,and the r1 value is 3.86 m M-1s-1 at p H=5.8 and the r1 value is 0.79 m M-1s-1 at p H=7.4.The r1 value of p H=5.8 is about 4.88 times than the r1 value of p H=7.4.The former of the magnetic resonance imaging is better significant than the latter of the magnetic resonance imaging.The rGO-MnO₂-PEG nanomaterials can be loaded with 131 I radiotherapeutic agents and have high radioactivity stability and can be used in subsequent in vitro and in vivo experiments.Cell experiments showed that rGO-MnO₂-PEG did not produce significant acute toxicity to cells at 100 ?mol/L.At the same 131 I drug concentration,131I-rGO-MnO₂-PEG produced significant acute toxicity to cells compared to free 131 I.In vivo experiments showed that 131I-labeled rGO-MnO₂-PEG nanomaterials were used for Gamma imaging of mouse tumors;131I-rGO-MnO₂-PEG drug delivery system had higher passive tumor enrichment effect and long blood circulation time.Radiotherapy of tumors can be achieved.In this paper,131I-labeled PEG-modified reduced graphene oxide nanocomposite?rGO-MnO₂-PEG?was used as a method to overcome the hypoxic microenvironment.At the same time,increase the effect of radioisotopes on cancer treatment.It was found that the 131I-rGO-MnO₂-PEG nanocomposite can obviously generate oxygen in the presence of hydrogen peroxide in solid tumor sites to overcome the tumor's hypoxic microenvironment.The treatment of animal cancer can also increase the effect of radioisotope therapy.The manganese dioxide nanomaterial catalyzes hydrogen peroxide and releases manganese ions?Mn2+?for use in nuclear magnetic imaging to achieve imaging-guided cancer treatment.This article provides a novel strategy that has good reference value for the future diagnosis and treatment of tumors.Contrast agents are important adjuvant drugs for MRI.Studies have shown that the rational use of nuclear magnetic contrast agents will not cause harm to human health,but also enhance the strength of tissue scan signals,so that the diagnosis of clinical conditions is more accurate.