Reductive Response And RGD Targeted GO Drug Delivery System And Anticancer Activity

Objective:In order to construct a drug carrier system which can reach tumor tissue actively in blood circulation and under the stimulation of high concentration of glutathione reducing response releasing anticancer drugs,then giving full play to anticancer effect.In this paper,reductive response and targeted Nano-graphene oxide Drug-loading system（RGPD）with good stability,biocompatibility,targeted and reduced response release was synthesised.Doxorubicin（DOX）was conjugated RGPD（RGPD-DOX）.Study on its anticancer activity.Drug delivery system can target and control releasing of drugs to reduce the damage to normal tissue and reduce the toxicity of traditional chemotherapy drugs.Methods:1.Targeted graphene oxide carrier with good biocompatibility was combined with amide condensation of the carboxyl group of the GO and the aminogroupofRGDandPEG-NH₂undertheconditionsof1-（3-dimethylaminopropyl）3-ethylcarbodiimidehydrochlorideand N-hydroxysuccinimide.The reductive response and targeted nano-graphene oxide drug carrier RGPD was combined with amide condensation of the amino group of PEG-NH₂ which has been grafted on graphene oxide and the carboxyl group of DTPA.2.Characterization of reductive target-targeted nano-graphene oxide drug carrier by infrared spectrum detection and analysis（FTIR）,X-ray photoelectron spectroscopy（XPS）,scanning electron microscopy（SEM）and Transmission Electron Microscopy（TEM）.3.The reductive response and targeted nano-graphene oxide drug-loading system（RGPD-DOX）was prepared by the carboxyl group on the functionalized graphene oxide drug carrier RGPD to bind to the amino group of DOX,and studyitsdrug-loadedanddrug-releasedperformancebyUV-vis spectrophotometry and dialysis methods.4.Studied the photothermal performance of the functionalized graphene oxide drug carrier RGPD by near-infrared photothermal irradiation.5.The in vitro cytotoxicity of RGPD on human liver cancer Hep-G2 cells and human normal liver cells 7702 was detected by MTT assay.6.Determined the inhibition of cancer cell growth after drug-loading system and drug-loading system combined with near-infrared hyperthermia by MTT.Results:1.The reductive response and targeted graphene oxide drug carrier（RGPD）was prepared and the structural morphology was identified by FTIR,XPS and SEM.2.The reductive response-targeted graphene oxide drug-loading system was prepared.When the amount of DOX was 5 mg,the loading efficiency of the carrier was 0.76 mg/mg.The release rate reached 88.72%under the simulated tumor environment in vitro（The glutathione concentration was 10 mM and PBS solution was pH=5.50）.3.When the carrier was irradiated with 808 nm near infrared laser at the same irradiation time,the higher concentration of the carrier was,the higher the temperature was.The carrier was irradiated with 808 nm near-infrared laser for5 min,when the carrier concentration was 0μg/mL,the temperature was 32°C,and when the carrier concentration was 0.78μg/mL,the temperature reached42°C.4.In vitro toxicity study,when the cells were incubated at a carrier concentration of 100μg/ml,the viability of human normal hepatocytes 7702cells was 85.24%.5.Reductive response and targeted nano-graphene oxide drug-loading system RGPD-DOX combined with photothermia had significant anticancer activity（p<0.05）.When the drug-loading system concentration was 1.56μg/mL,the inhibition rate of Hep-G2 in tumor cells was 55%,while the drug-loading system combined with photothermia therapy group inhibition rate of Hep-G2 in tumor cells was 78%.Conclusions:The drug carrier RGPD with good stability and biocompatibility,targeted,and reduced response release is prepared,and its special photothermal properties and drug-loading properties are evaluated.In vitroexperimentalstudies,thedrug-loadedsystemcombinedwith photothermotherapy has better anticancer activity.