Application Of Graphene-based Nanohybrid Materials In Tumor Multimodal Imaging And Therapy

Graphene is a new carbon material which is composed of carbon atoms with single sheet structure.Graphene is a two-dimensional material honeycomb structure with sp2 carbon atom hybrid orbital,whose thickness is only about one carbon atom.Graphene oxide?GO?is an important derivative of graphene,also known as functionalized graphene.Its structure is roughly the same as that of graphene,but the two-dimensional surface of GO is attached with some functional groups.GO has a large specific surface area and abundant surface defects,so the inorganic nanoparticles can be anchored to the surface of graphene oxide by in situ growth or binding method.The stability and controllability of GO in vivo can be improved by surface modification,which can bring excellent bio-compatibility to GO based nanohybrid materials.Nanohybrid materials of graphene oxide can be used not only for photothermal therapy of tumor,but also as a nanocarrier of drugs and gene for delivery,or as contrast agent in biological imaging,including CT imaging,magnetic resonance imaging,photoacoustic imaging,etc.At present,there are a large number of articles about the wide application of GO and its derivatives in bio-medicine.In this thesis,GO-based nanohybrid materials were synthesized by in situ growth of Mn WO₄ or Bi₂Se₃ nanoparticles on the surface of GO,and the surface modification with polyethylene glycol?PEG?or polyvinylpyrrolidone?PVP?was simultaneously carried out by “one pot” method.The conbination of doxorubicin hydrochloride?DOX?and nanohybrid materials was obtained by ?-? interaction and electrostatic interaction.We can achieve GO-based nano-hybrid materials with synergistic effect of photothermal/chemo therapy.In the first Chapter,we reviewed the structure,properties,preparation methods,surface functionalization of graphene oxide and its applications in biological imaging and tumor therapy.In the second Chapter,we studied the preparation and characterization of GO/MnWO₄/PEG nanohybrid material and their application in biological imaging and tumor therapy in vitro and in vivo.The GO/MnWO₄/PEG nanohybrid material synthesized by high temperature heating showed good morphology,small size and good dispersibility.Solution level characterization of the material showed high absorption under the near infrared laser,and the material showed good capability of photothermal conversion after irradiation.GO/MnWO₄/PEG nanohybrid material can be loaded with an anti-cancer drug DOX on the surface,and the drug was released more in acidic solution.With the photothermal effect after irradiation,the ability of drug release will be enhanced.At the same time,GO/MnWO₄/PEG nanohybrid material showed good MR/CT/PA imaging performance in vitro and also achieved good imaging effect in vivo.The results of in vitro experiments revealed that GO/MnWO₄/PEG showed good biocompatibility and had synergistic photothermal/chemo effect on 4T1 cells after drug loading.The GO/Mn WO₄/PEG nano-hybrid material was applied to the therapy of tumor bearing mice based on its good biocompatibility and therapeutic effect in vitro,and good photothermal/chemo synergistic effect was obtained.Therefore,GO/Mn WO₄/PEG nanohybrid material can be used in vivo multi-mode imaging and photothermal/chemo synergistic therapy.In the third chapter,we studied the preparation and characterization of GO/Bi₂Se₃/PVP nanohybrid material and its applications in photothermal therapy and CT/PA imaging in vivo.The material was injected into the tumor-bearing mice by tail vein,and then the mice were scanned to obtain CT images.The contrast enhanced imaging was observed in the tumor site of the mice.The photoacoustic imaging of GO/Bi₂Se₃/PVP nanomaterial in vitro showed a good capability.With the increase of the material concentration,the image contrast was enhanced.Then,GO/Bi₂Se₃/PVP was applied to the photoacoustic imaging of the tumor-bearing mice,which also shows favorable imaging results,indicating that the material can be used as CT/PA dual-model imaging contrast agent.The in vivo cancer photothermal therapy experiments were carried out by intravenously injection of the material,and ideal cancer photothermal ablation effect were obtained.Therefore,the GO/Bi₂Se₃/PVP nanocomposite material can be used in CT/PA imaging and cancer photothermal therapy.In the fourth chapter,the important experimental data and results obtained in this work were summarized.Finally,we show the outlooks about the further applications of GO-based nanomaterials in the future.