Preparation Of Functionalized Nano - Sized Graphene And Its Tumor - Targeting Radionuclides And Optical Molecular Images

Nanographene oxide has become a popular research topic in nanomedicine due to its unique properties such as ultra-high surface-to-volume ratio and great photo-thermal effect. It contains a large amount of reactive chemical groups, including carboxy group, carbonyl group, hydroxyl group and epoxy group, which enable its easy biological and chemical functionalization and excellent biocompatibility and therefore high potential applications in biomedical field. This paper mainly studies different sizes of nanographene oxide prepared by using the improved Hummers method, and the covalent modification of PEG and fluorescent molecular of Cy5.5 with nanographene oxide. The optimized nanographene oxide complex was obtained by in vitro cell assays, which was further conjugated with target molecules of folic acid(FA), and then labeled by nuclide 125 I and fluorescent molecular of Cy5.5 to form 125I-n GO-PEG-FA and n GO-PEG-Cy5.5-FA as nuclear and optical molecular imaging probe, respectively. The tumor targeting and biological properties in vivo were investigated by small animal nuclide and optical imaging of live tumor models. The full text is divided into three chapters.In the first chapter, the preparation, structure and properties of graphene, the surface modification methods of graphene, and the applications of graphene oxide in the biological field were summarized. At the same time, the applications of nanographene oxide in nuclear and optical molecular imaging were also introduced. Finally, the research ideas of this paper were proposed.In the second chapter, firstly the different sizes of nanographene oxide prepared by using the improved Hummers method, and covalent modification of PEG on the nanographene oxide surface were investigated. Nanographene oxide complex was optimized by in vitro cell assays and confocal laser experiments, which was based on the conjugation of fluorescent molecular of Cy5.5 with the amino groups of PEG. After further studies and evaluations through the applications of cell and small animal, the optimized nanographene oxide complex was further conjugated with target molecules of folic acid(FA), and then labeled by nuclide 125 I and fluorescent molecular of Cy5.5 to form FA-targeted functional nanomaterials. The in vitro experiments showed that nanomaterials had very low cytotoxicity. Confocal laser experiments showed that nanomaterials was up taken into the 4T1 cells with overexpressed FA receptors more efficiently than A549 cells with low-expressed receptors. The target nanomaterials n GO-PEG-Cy5.5-FA and 125I-n GO-PEG-FA was injected into tumor mouse by tail vain, then investigated by small animal SPECT/CT and optical imaging. The nanomaterials n GO-PEG-Cy5.5-FA and 125I-n GO-PEG-FA were all highly accumulated into the tumor sites compared to the blocking group, which indicated that the materials has tumor folate receptor targeting property. Histological assessment of tissues was studied to evaluate the toxicity of the material, which showed that nanographene oxide had no obvious toxicity and good biocompatibility. Therefore, the folic acid-funtionalized nanographene oxide exhibits good folate receptor targeting capabilities, which could be an ideal nanocarrier of multi-modal molecular imaging probe for folate receptor-positive tumor and has great application potentials in cancer theranostics.In the third chapter, the results obtained in this work were summarized, and the application prospects of the nanographene oxide in the biomedical fields were also mentioned.