Preparation Of Graphene-Based Nanocomposites And Their Applications In Bio-imaging

Graphene is a typical sp carbon nanomaterial attracting extensive attentions in multidisciplinary studies because of its unique physicochemical properties. This work focuses on the preparation and characterization of multifunctional graphene-based nanocomposites and their applications in bio-imaging. Generally, it is difficult to achieve fluorescent graphene-quantum dots (QDs) nanocomposites because graphene quenches the fluorescence of the QDs. Regulating the space between QDs and graphene, and passivating the surface of QDs are adopted to protect the fluorescence of QDs being quenched by graphene. The prepared fluorescent graphene-QDs nanocomposites are applied in cancer cell imaging and therapy. Then, GO-PEG-β-FeOOH nanocomposites are prepared by in situ growth of β-FeOOH nanorods onto PEGylated graphene oxide (GO) and used as a new contrast agent in magnetic resonance imaging (MRI). It exhibits a record ultra-high transverse relaxivity (r2) value compared with those for hitherto reported β-FeOOH based MRI contrast agents. The major achievements in the present thesis include the following:1. We have demonstrated direct conjugation of graphene (reduced graphene oxide, RGO) with QDs via a bridge of bovine serum albumin (BSA). This provides a novel highly fluorescent nano probe for the first time. BSA capped QDs are firmly grafted onto polyethylenimine (PEI)/poly(sodium 4-styrenesulfonate) (PSS) coated RGO (graphene-QDs) via electrostatic layer by layer assembly. The strong luminescence of the graphene-QDs provides a potential for non-invasive optical in vitro imaging. The graphene-QDs are used for in vitro imaging of live human carcinoma (Hela) cells. Graphene-QDs could be readily up-taken by Hela cells in the absence of specific targeting molecules, e.g., antibodies or folic acid, and no in vitro cytotoxicity is observed at 360μg mL-1 of the graphene-QDs. The results for the imaging of live cells indicated that the cell-penetrating graphene-QDs could be a promising nano probe for intracellular imaging and therapeutic applications.2. We prepared a novel quantum-dot-conjugated graphene, i.e., hybrid SiO2-coated quantum dots (HQDs)-conjugated graphene, for targeted cancer fluorescent imaging, tracking, and monitoring drug delivery, as well as cancer therapy. The hybrid SiO2 shells on the surface of QDs not only mitigate its toxicity, but also protect its fluorescence from being quenched by graphene. By functionalizing the surface of HQDs-conjugated graphene (graphene-HQDs) with transferrin (Trf), we developed a targeted imaging system capable of differential uptake and imaging of cancer cells that express the Trf receptor. The widely used fluorescent antineoplastic anthracycline drug, doxorubicin (DOX), is adsorbed on the surface of graphene and results in a large loading capacity of 1.4 mg mg-1. It is advantageous that the new delivery system exhibits different fluorescence color in between graphene-HQDs and DOX in the aqueous core upon excitation at a same wavelength for the purpose of tracking and monitoring drug delivery. This simple multifunctional nanoparticle system can deliver DOX to the targeted cancer cells and enable us to localize the graphene-HQDs and monitor intracellular DOX release. The specificity and safety of the nanoparticle conjugate for cancer imaging, monitoring, and therapy has been demonstrated in vitro.We have also demonstrated in situ growth of β-FeOOH nanorods onto PEGylated graphene oxide sheets to produce a nanocomposite, e.g., GO-PEG-β-FeOOH. This nanocomposite exhibits a record ultra-high r2 value of 303.81 mM-1 s-1, that is,>60 times higher than those achieved by hitherto reported β-FeOOH based MRI contrast agents. This well facilitates its practical use as a contrast agent for in vivo MR imaging. PEG on the surface of the GO nanocomposite improved the colloidal stability in aqueous medium. In addition, in vitro cell viability tests demonstrated that GO-PEG-β-FeOOH has minimal cellular toxicity. GO-PEG-β-FeOOH has been used for loading DOX with a capacity of 1.35 mg mg-1, which exhibits high efficiency in Hela cell apoptosis. These results indicated that GO-PEG-β-FeOOH provide an effective alternative to the existing nanoparticle based contrast agents for non-invasive in vivo MR imaging and cancer therapy.