Functionalization Of Graphene Quantum Dots And Their Applications In Bioimaging And Drug Delivery

As the lasted member of graphene families, graphene quantum dots(GQDs) have excellent performances conferred by graphene. Besides, GQDs exhibit additional marvelous properties due to quantum confinement and edge effects. So they have attracted more and more attention from scientists in aspects of chemistry, physics, biology, and so on. Because of the large surface and rich functional groups on the surface, GQDs can be used as a carrier. The surface of GQDs has been modified with ligands of specific functions or loaded with doxorubicin. The functionalized GQDs show great promise in biomedical diagnosis and treatment field. In the thesis, GQDs with excellent properties were synthesized by using carbon fiber and a simple chemical cutting method, and subsequently, we studied its stability and fluorescence proporties. Then GQDs were functionalized for multi-mode bioimaging and drug delivery functions. The full paper is divided into four chapters.In the first chapter, we summarize the preparation methods, properties and applications of GQDs. Finally, the research ideas of this thesis are proposed.In the second chapter, the DOX/GQDs-Gd multifunctional nanomaterial was prepared and characterized. We also investigated its effect of cancer therapy in vitro and the fluorescence/magnetic dual-mode imaging function. In this experiment, GQDs, which were synthesized by chemical cutting method, have uniform size and good dispersion and biocompatibility. What’s more, it can be stably dispersed in physiological solution for a long time. The stability of fluorescence was almost unaffected by pH, the concentration of sodium chloride and illumination time. The resulting GQDs-Gd still has a good stability, biocompatibility and low biological toxicity. It shows good fluorescence property and ideal magnetic resonance contrast effect in solution or cellular level. Meanwhile, it is also a good drug delivery carrier and has a pleasurable therapeutic effect in vitro. Accordingly, DOX/GQDs-Gd combines fluorescence, magnetic resonance imaging and chemotherapy into one system, supplying a new platform for the treatment and diagnosis of cancer.In the third chapter, the GQDs-PEG-TAT multifunctional nanomaterial was prepared and characterized. We also evaluated its biological safety and then loaded doxorubicin on the nanomaterial to study its targted therapeutic effect in vitro. The smaller sized GQDs were obtained by increasing the reaction temperature, and they showed good morphology and clearly visible lattice structure. Then we modified double amino polyethylene glycol, TAT polypeptide and doxorubicin one after another on the surface of GQDs. Protein gel electrophoresis was used to certify that the TAT polypeptide was successfully immobilized on the GQDs-PEG-NH2 by covalent interaction. The methyl thiazolyl tetrazolium(MTT) assay was performed to evaluate the toxicity of GQDs-PEG-TAT in vitro, making sure that the toxicity of the material is low enough to be used for biological application. We used a confocal laser scanning microscopy to observe that GQDs-PEG-TAT could target the nucleus of He La cells, and it also exhibits a significant effect in cell therapy experiment. The results show that GQDs-PEG-TAT is expected to be a new type of multifunctional targeting nanomaterial.In the fourth chapter, we summarize the experimental data and results obtained in this work. Finally, we show the outlooks about the problems of GQDs and the further applications of GQDs based nanomaterials in the fields of biology.