Preparation Of Non-Covalently Modified Nanocomposites Based On Graphene Oxide And Its Application In Drug Delivery

Cancer remains in recent years a challenging and devastating health problem in the world.In order to improve the therapeutic efficiency of chemotherapeutic drugs and to decrease the adverse effects,an assortment of anti-cancer drug delivery carriers have been investigated.Among these,nanomaterial-mediated drug delivery systems have attracted numerous attention.Among the various nanomaterials,graphene oxide has been exploited with advanced properties,such as water solubility,large specific surface area available for high drug loading,therefore,it's not surprising that GO has received tremendous attention in nanomedicine and biomedical field.While GO sheets can yield a variety of advantages,the exploration of the material was hampered by poor solubility of the sheet in biological environment.Therefore,to improve its solubility in physiological environments has became the key to solve the problem.A popular way to stabilize GO in physiological conditions is surface modification.Layer-by-layer(Lb L)nanoarchitecture shows great potential for the nanoparticle surface functionalization.The method of layer-by-layer technique involves the step-wise deposition of polyelectrolytes with opposite charges on the surfaces of the particles to form core-shell nanoparticles.However,the Lb L deposition of charged polyelectrolytes on GO nanosheets for the application of anti-cancer drug delivery is still in its infant phases.In this paper,we used two oppositely charged polyelectrolytes respectively,chitosan(CS)and sodium alginate(SA),chitosan(CS)and dextran(Dex),protamine(PRM)and sodium alginate(SA)as templates,using Lb L nanoarchitecture to synthesize GO-CS-SA,GO-CS-Dex,GO-PRM-SA nanocomposites respectively.The functionalization was verified by FTIR,zeta potential and AFM analysis.Then,the stability and non-specific protein adsorption of nanocomposites were studied.Finally,the nanocomposites were loaded with anti-cancer drug doxorubicin(DOX),then the drug loading,drug release and cytotoxic behavior were investigated.The results are as follows:1.we used GO as the matrix,two oppositely charged polyelectrolytes,CS and SA,CS and Dex as templates to synthesize GO-CS-SA,GO-CS-Dex nanocomposites through Lb L technology.The composites were verified by FTIR,AFM,Zeta Potential and TGA analysis.The results indicated that CS and SA,CS and Dex successfully deposited on the surface of GO.The stability test and non-specific protein adsorption test showed the modification of CS/SA and CS/Dex not only improved the dispersity and stability of GO but also decreased the non-specific protein adsorption in physiological conditions.2.The drug loading experiment showed that the GO-CS-SA and GO-CS-Dex composites had higher drug loading capacity.The drug release experiment showed that the GO-CS/SA and GO-CS/Dex loaded with DOX displayed dramatically p H-responsive drug release behavior.Cellular uptaken studies showed that the nanocomposites could be uptaken by MCF-7 cancer cells and located in the cytoplasm.The in vitro cytotoxicity assay indicated that the pure GO nanocomposites induced no obvious inhibitory effects against MCF-7 cells,however,the DOX-loaded GO-CS/SA and GO-CS/Dex complex had enhanced cell toxicity against the cells.3.By selecting GO,PRM,and SA as raw materials,we successfully synthesized GO-PRM-SA nanocomposites by physical adsorption.The composites were verified by FTIR,AFM,Zeta Potential and TGA analysis.The results suggesteded that PRM and SA successfully deposited on the surface of GO.The stability test and non-specific protein adsorption test showed that the modification of GO by PRM and SA not only improved the solubility of GO but also decreased the non-specific protein adsorption in physiological conditions.Drug loading experiment indicated that the complex had a high drug loading rate and the drug release experiment showed that the composites loaded with DOX had a significant p H-responsive drug release behavior.Finally,The MTT cytotoxicity assay showed that GO-PRM-SA loaded with DOX had significant cytotoxicity to MCF-7 cells.