Synthesis Of Functionalized Graphene Oxide And Its Application In Drug Delicery And Magnetic Resonance Imaging

Since it was discovered in2004, graphene has attracted more and moreattention. Previous studies have found that the derivatives of graphene oxide havegood solubility in water, good biocompatibility and no obvious toxicity. Theseadvantages expand the application of graphene in various fields. This paper mainlystudies covalent modifications of target molecules of hyaluronic acid （HA） on thegraphene surface, the formed HA grafted graphene oxide （GO-HA） can be used asdrug carrier materials. We further research the biocompatibility of GO-HA and thetreatment effect of drug-loaded GO-HA on tumor-bearing nude mice. Afterwards,manganese ferrite nanoparticles were in situ grown on the surface of graphene oxide（GO） to produce GO/manganese ferrite （GO/MnFe₂O₄） hybrid nanomaterials. Theapplication of the GO/MnFe₂O₄as T2-weighted magnetic resonance imaging （MRI）contrast agents and its in vivo behavior were further studied. The full text is dividedinto four chapters.In the first chapter, the structure and properties of the graphene, the surfacemodification methods of graphene with nanoparticles, and the applications ofgraphene and graphene oxide in the biological field were summarized. At the sametime, we also introduce the application of graphene oxide in MRI. Finally, theresearch ideas of this paper were proposed.In the second chapter, the surface of GO was covalently modified with adipicacid hydrazide （AAH）, and then the amino groups of GO-AAH was used to furtherconjugate HA to form GO-HA drug carrier nanomaterials. The thickness of graphene oxide was about1.0nm, the average size of GO was about300nm. The drug loadedcapacities of GO-HA in different concentration of hydrophilic anti-cancer drugdoxorubicin （DOX） and hydrophobic drug camptothecin （CPT） were studied. WhenDOX concentration was1mg/mL, loading capacity of DOX on GO-HA reached amaximum value of800mg/g. For CPT, when the concentration of CPT was80μg/mL,a maximum drug loading of145mg/g was obtianed. Furthermore, the co-loading ofDOX and CPT on GO-HA to form GO-HA/CPT/DOX materials was also studied. It wasfound that, under a saturated loading ratio of CPT on GO-HA, the loading ratio of DOXincreased gradually with the concentration of DOX. When the concentration of DOXwas0.1mg/mL, the adsorption of DOX on GO-HA/CPT reached the maximum valueof400mg/g. The in vitro experiments showed that GO-HA had very low cytotoxicityand hemolysis activity. Confocal laser experiments showed that GO-HA was up-takento the HeLa cells with overexpressed HA receptors more efficiently than L929cellswith low-expressed receptors by the receptor mediated endocytosis. The materialswas injected into kunming mouse by tail vain, then the blood was collected atdifferent time point, and then the blood smear, biochemical analyses and histologicalassessment of tissues was studied to evaluate the toxicity of the material. The resultsshow that GO-HA has no obvious toxicity and good biocompatibility. ThenGO-HA/DOX was used to treat HeLa tumor-bearing mice, and the treatment effectwas assessed. After the treatment, compared to the control group, the relativelytumor volume showed slower growth and the weight loss of the mice is not obvious,showing that GO-HA/DOX has significant therapeutic effect. Therefore, the GO-HAcan be used as an effective drug delivery material and is expected to do furtherresearch in the treatment of cancer.In the third chapter, we use the high temperature pyrolysis method toprepare GO/MnFe₂O₄hybrid nanomaterials. The resulting hybrid materials showedsuperparamagnetism, good hydrophilicity, low toxicity, negligible hemolysis effectand obvious MRI contrast enhancement effect on cancer cells. In vivo MRIexperiments show that after intravenous injection via tail vein, T2weighted imaging signal of liver and spleen quickly reduced, indicating that the trace of GO/MnFe₂O₄in vivo can be tracked by MRI technology and the sample can be used as an MRIcontrast agents. The study on the mice tumor MRI showed that, over a period of time,the material was gathered at the tumor site, indicating that GO/MnFe₂O₄may beused a cancer diagnosis material. In addition, a more in-depth exploration was doneto study the in vivo distribution, pathology analysis and metabolic pathways ofGO/MnFe₂O₄. The results show that the material can be uptaken by liver, lungs andspleen, and can be excreted from the elimination organs of liver and kidneys.Therefore, GO/MnFe₂O₄hybrid materials have good biocompatibility and canprovide useful information for their future biological application.In the fourth chapter, the important results obtained in this work weresummarized, and the application prospects of the prepared materials in thebiomedical fields were also mentioned.