Fabrication And Anti-cancer Mechanism Of Functional Graphene Oxide

Graphene has many excellent physical and chemical properties, such as special molecular structure, large surface area, excellent optical, electrical, mechanical and thermal performance. Oxidized graphene(NGO) has good biocompatibility and water solubility. Moreover, NGO has low toxicity. The excellent properties of graphene oxide make it a promising biological material. In recent years, it is hotspot that graphene oxide as a nanometer carrier is applied to anticancer drugs. Graphene oxide loaded with the anticancer drugs could enhance the anticancer efficacy of anticancer agents and reduce their toxic side effects. In this dissertation, we constructed a cancer-targeted NGO by using polyethyleneimine(PEI) and transferrin(Tf) as the surface decorators. Moreover, the anticancer activities triggered by the functional nano drug delivery systems in vitro were also investigated in this study. The main results include:1、Construction of bioresponsive nano drug delivery systems could enhance the anticancer efficacy of anticancer agents and reduce their toxic side effects. Nano-graphene oxide(NGO) is a newfangled nanomaterial and its good biocompatibility and low toxicity make it a promising material for drug carrier substance. Herein, we constructed a cancer-targeted NGO by using transferrin(Tf) as the surface decorator, and demonstrated its use as a bioresponsive drug delivery system of phenanthroline small molecules. The phenanthroline(p-HPIP) was successfully and efficiently loaded into NGO via π-π stacking and electrostatic interaction. This nanosystem(Tf-NGO@HPIP) drastically enhanced the cellular uptake and retention of p-HPIP in cancer cells, and hence strengthened its anticancer ability, but not normal cells. Tf-NGO@HPIP was internalized through receptor-mediated endocytosis and triggered pH –dependent drug release under acidic environments and with the presence of cellular enzymes. Moreover, Tf-NGO@HPIP shows unprecedented enhanced cytotoxicity toward cancer cells by triggering cell apoptosis through activation of p38 and JNK, and inactivation of ERK and AKT. The intracellular nanoparticles also triggered the overproduction of intracellular superoxide generation to induce DNA damage and activation of p53 pathway. Taken together, this study demonstrates a good strategy for construction of bioresponsive NGO nano drug delivery systems and the use as efficient anticancer drug carriers.2、A NGO-complexes nanometer system was contructed. Moreover, PEI was used to improve its biocompatibility. Research shows that the nano system has good water solubility and biocompatibility after the PEI modification. The nano system has effectively solved the biocompatibility and stability of metal complexes with anticancer effect. After modified by targeted ligands, the nano system Tf-NGO@complexes has dual functions: pH response and targeted feature. The dual-functional nano system Tf-NGO@complexes exhibited higher anticancer effect yet lower side effects than metal complexes alone. This effect is closely related to the enhancement of cellular uptake and cellular drug retention. The nano system Tf-NGO@complexes enhanced drug absorption in cancer cells but not in normal cells. The tumor spheroids experiment, the migration and invasion experiment have proved that Tf-NGO@complexes possessed excellent penetrating ability and higher inhibitory effects than those of free complexes. Moreover, the selective cellular uptake endowed the nanosystems with enhanced cytotoxic effects against cancer cells through induction of oxygen species(ROS)-mediated apoptosis. This study provides useful information for solving the poor solubility of Pt/Ru complexes under physiological conditions and low permeability retention effect in tumor cells.3、A functional nanosystem Tf-NGO@BSBD was constructed by NGO loaded with selenium compounds, The nanosystem Tf-NGO@BSBD has much higher anticancer efficacy against cervical cancer cells(Caski,Siha,Hela),but no toxicity for normal cells(NIH-3T3). The functional nanosystem Tf-NGO@BSBD enhanced the cellular uptake and cellular drug retention in cancer cells, and triggered ROS upregulation to induce the cell apoptosis. These results showed that Tf-NGO@BSBD improved the efficacy and safety of free selenium compounds.