Development Of A Compound Graphene Oxide Nanocarrier For Hepatic Carcinoma Chemo-Photothermal Combination Therapy

In recent years,as a monolayer of two-dimensional carbon nanomaterials,the study graphene oxide has been made significant progress in the field of biomedicine due to its good biocompatibility,easy modification,durg transport in vitro or vivo,photo-thermal effects,unique physical and chemical properties.Moreover,there is potential for further development of graphene oxide.In this paper,we designed a functionalized graphene oxied nanomaterials,based on the modification of material properties and characteristics,because of its large specific surface area,the capacity of aromatic molecules,π-πstacking interaction and hydrogen bond interaction,which applied in chemo-photothermal synergistic treatment and gene delivery.All these results showed that functionalized graphene nanomaterials have potential applications in the biomedical field.Following are the main contents of our work:1.To build a Moderate size,ultra-stable,biocompatible chemo-photothermally therapeutic reduced graphene oxide nanocompositesIn this chapter,we used an inexpensive,convenient and rapid method to amidate graphene oxide with a 1:1 mixture of branched high molecular polyethyleneimine(25K)and low molecular weight polyethyleneimine(1.8K),then reduced with methoxy polyethylene glycol amino group in 90℃water bath to produce a composite polyethyleneimine and polyethylene glycol modified nano-graphene oxide.The samples were characterized by atomic force microscopy(AFM),Zeta potential meter,UV-vis spectroscopy,Fourier transform infrared spectroscopy(FT-IR).The reduced graphene oxide has a size of 100-300 nm,a thickness of 1.5-2.5 nm and a potential of+23.4m V.Under the near-infrared 3W/cm~2 power irradiation,the reduced graphene oxide showed good photothermal effect and photostability,after loading of doxorubicin did not change the photothermal performance.Under the fluorecence spectrophotometry,drug loading and release experiments,the reduction of graphene oxide can efficiently load doxorubicin up to 81.56%,and the drug can be released up to50%in 48 hours at p H=5.3.The reduction of graphene oxide provides a good foundation for subsequent biomedical research.In addition,the reduced graphene oxide conjugated with enhanced green fluorescent protein gene(EGFP),treated in SMMC-7721 cells for transfected.Agarose gel electrophoresis showed that thepositively charged polyelectrolyte reduced graphene oxide completely combined with EGFP when the N/P was 10,and the potential still showed a positive value.In gene transfection,reduced graphene oxide conjungated with EGFP exhibit up to 78%transfection efficiency at a N/P of 20.This work shows that the reduced graphene oxide can be used as a carrier for excellent gene delivery.2.The reduced graphene oxide nano-system applied to chemical and photothermal combination therapy of hepatoma carcinomaIn this chapter,we investigated the synergistic effect of chemical and photothermal effects by using doxorubicin-loaded reduced graphene oxide treated in hepatoma SMMC-7721 cells and mouse tumor models under the irradiation of near infrared laser(NIR).Cell uptake experiments showed that reduced graphene oxide can carry doxorubicin into the cells and release efficiently in the lysosomes and eventually enter the nucleus.Light irradiation promoted drug release without affecting the intracellular uptake of reduced graphene oxide.Cytotoxity experiments show that reduced graphene oxide nano-system showed a huge killing effect on liver cancer cells.In vivo experiments show that reduction of graphite oxide eliminated mouse tumors with photothermal effect and doxorubicin chemotherapy at 20 days,resulted in a outstand-ing therapeutic effect.