Fabrication Of Graphene Oxide Based Nanocomposites And Its Applications On Drug Delivery And Bioimaging

Graphene is a two-dimensional crystal of sp2-hybridized carbon atom arranged in six-membered rings. Grephene has sparked tremendous interest on the filed of materials science and nanodevice due to their unique magnetic, optical and chemical properties. Graphene oxide(GO), a derivative of graphene, prepared from natural graphite has attracted great attentions in biomedical applications such as drug and gene delivery, bioimaging, cancer diagnosis and therapy because of its good biocompatibility, large surface area, nanoscale size and abundant surface functional groups. There are a lot of groups reported that GO can effectively delivery drug for tumor chemotherapy and radiolabeld GO can be a platform for in vivo tumor imaging and therapy.In this thesis we construct a few nanocomposites that based on GO nanomaterials for drug or gene delivery to cancer cells and in vivo tumor imaging. The main contents are as follows:(1) Using a simple, efficient and convenient method to prepare graphene oxide nanosheets(NGO) with good biocompatibility, large surface area and abundant functional groups(-COOH, OH) on the surface. And almost all the nanocaomposites in the following chapters are based on this NGO.(2) Based on NGO have been synthesized, we constructed a highly biocompatible and hydrophilic shell on individual gold nanoparticle and nanorod surface by encapsulating nanoparitcles or nanorods in GO nanosheets and used these core/shell hybrids for the first time as gene vectors to delivery p DNA into He La cells. It exhibited good DNAbinding capacity and condensed plasmid DNA into nanoscale particles(150 nm). In vitro gene transfection tests demonstrated that GOpolyethylenimine/gold nanoparticles(GOPEI-Au NPs) presented much lower cytotoxicity and comparable transfection efficiency(65% efficiency and 9 0% viability) with commercial PEI 25 k Da in He La cells, which can be attributed to the small size and spherical structure facilitating cellular uptake. Considering the excellent dispersibility, biocompatibility and high transfection efficiency of GOPEI-Au NPs, their applications can be extended to si RNA delivery and photothermal therapy.(3) A novel nanostructure with gold nanorods(Au NRs) encapsulated in NGO shells is developed to be an ultraefficient chemophotothermal cancer therapy agent. The NGO shells decrease the toxicity of surfactant-coated Au NRs and provide anchor points for the conjugation of hyaluronic acid(HA). The HA-conjugated NGO-enwrapped Au NR nanocomposites(NGOHA-Au NRs) perform higher photothermal efficiency than Au NRs and have the capabili ty of targeting hepatoma Huh-7 cells. NGOHA-Au NR is applied to load doxorubicin(DOX), and it exhibits p H-responsive and near-infrared light-triggered drug-release properties. Chemophotothermal combined therapy by NGOHA-Au NRs-DOX performs 1.5-fold and 4-fold higher targeting cell death rates than single chemotherapy and photothermal therapy, respectively, with biosafety to nontargeting cells simultaneously.(4) We developed double-PEGylated biocompatible reduced graphene oxide nanosheets anchored with iron oxide nanoparticles(RGO-IONP-1stPEG-2ndPEG). The nanoconjugates exhibited prolonged blood circulation half-life(~27.7 h) and remarkable tumor accumulation(15.5 %ID/g) via enhanced permeability and retention(EPR) effect. Due to strong near-infrared absorbance and superparamagnetism of RGO-IONP-1st PEG-2nd PEG, multimodality imaging combining positron emission tomography imaging(PET) with magnetic resonance imaging(MRI) and photoacoustic(PA) imaging was successfully achieved. The promising results suggest great potential of these nanoconjugates for multi-dimensional and more accurate tumor diagnosis and therapy in the future.(5) By using surfactant cetyltrimethylammonium chloride(CTAC) and oleic acid we synthesize Au NRs with high yields. And we coated a biodegradable mesoporous silica layer on the surface of Au NRs by take advantage of residual CTAC molecules on the surface. Biodegradable mesoporous silica layer coated Au NRs(Au NRs@b MSN) can chelator-free label isotope 89 Zr due to the deprotonated silanol groups. After conjugated PEG to surface, Au NRs@b MSN-PEG has been used as a nonoplarform for in vivo tumor imaging and photothermal therapy, and got a remarkable PET imaging signal(9.5 %ID/g) in tumor area.