Preparation Of Graphene Quantum Dots And Its Application In Biological Imaging And Drug Delivery

As a new member of graphene family,graphene quantum dots(GQDs),inherit many excellent performance of graphene,such as the specific surface area,higher carrier migration rate and so on.Moreover,GQDs show excellent photoluminescence,low cytotoxicity and other characteristics due to their size effect,quantum confinement effect and edge effect.These characteristics of GQDs make them widely used in the field of biomedicine.In this paper,we have systematically studied the preparation and fluorescence properties of GQDs and nitrogen,sulfur,phosphorus,boron doped GQDs.The applications of GQDs in biological imaging and drug delivery were further discussed.The main contents of this paper are divided into the following parts:1.We synthesized GQDs by the method of acid oxidation,with the pyrolysis of oxidized graphite as raw materials and characterized the structure,morphology and fluorescence properties of GQDs systematically.The results showed that,the GQDs had uniform sizes and their average diameter was 3.7nm.The GQDs had stable fluorescence properties in the pH range of 3 to 11 and the fluorescence quantum yield(QY)of GQDs was 0.8%.Because the surface of GQDs was abundant in oxygen-containing functional groups,the water solubility of GQDs was better.2.In order to further improve the QY of GQDs,nitrogen-doped GQDs(N-GQDs),sulfur-doped GQDs(S-GQDs),phosphorus-doped GQDs(P-GQDs)and boron-doped GQDs(B-GQDs)were prepared by using GQDs as C source and melamine,dibenzyl disulfide,triphenylphosphine,and boric acid as N,S,P,and B sources,respectively-.The structure,morphology and fluorescence properties of those four kinds of Doped-GQDs were characterized systematically,and the effects of elemental doping on the photoluminescence properties of GQDs were further discussed.The results showed that the average diameters of N-GQDs,S-GQDs,P-GQDs and B-GQDswere 2.3nm,1.7nm,3.2nm,2.8nm,respectively,which were smaller than GQDs.Compared with the fluorescence spectra of GQDs,at the same excitation wavelength,the emission peaks of N-GQDs and S-GQDs showed blue-shifted,while P-GQDs and B-GQDs showed red-shifted.The QY of N-GQDs,S-GQDs,P-GQDs and B-GQDs were 15.8%,1.28%,1.52% and 1.68%,respectively,which were higher than that of GQDs.The effect of elemental doping on the fluorescence properties of GQDs can be attributed to the change of structural defects,surface functional groups,and interactions among carbon atoms with oxygen and doping atoms.3.Polyethylene glycol(PEG)functionalized GQDs(GQDs-PEG)were preparedby hydrothermal method with PEG as surface passivation agent.The physiological and environmental stability,cytotoxicity and cell imaging properties of GQDs and GQDs-PEG were compared.The results showed that,both GQDs and GQDs-PEG had no obvious toxicity to two cell models of U251 cells and lung cancer Hepg2 cells in the concentration range of 2.5-200?g/mL.The results of cell fluorescence imaging showed that GQDs and GQDs-PEG could enter the whole cell with high fluorescence recognition.However,the QY of GQDs-PEG was 3.7%,which was significantly higher than GQDs,and its physiological stability was significantly better thanthat of GQDs.Therefore,GQDs-PEG are more suitable for biomedical applications than GQDs.4.A targeted drug delivery system(DOX-GQDs-RGD)had been setted up by using GQDs as drug carriers and arginine-glycine-aspartate(RGD)peptide as connected targeting molecule.The anti-cancer drug(DOX)was loaded by hydrogen bonding and ?-? conjugation.The feasibility of GQDs as a drug carrier was studied by vitro drug release behavior,cytotoxicity evaluation and cell imaging experiment.Theresults showed that the drug loading of DOX-GQDs-RGD was 54.6%,and the release rate of DOX in the environment of pH=5.0,was significantly higher than that of pH=7.4.Due to the targeted selectivity of RGD to tumor cells,the killing effect of DOX-GQDs-RGD on cancer cells was much better than that of free DOX.Cell imaging experiments showed that we can locate the carrier and track DOX release simultaneously with the help of the inherent fluorescence of GQDs and DOX,The results confirmed that GQDs have a promising application prospect in the field of drug delivery.